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OBJECTIVES: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time. MATERIALS AND METHODS: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels. RESULTS: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels. CONCLUSIONS: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.
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Biomarcadores , Índice Vascular Cardio-Tobillo , Mediadores de Inflamación , Trasplante de Riñón , Valor Predictivo de las Pruebas , Calcificación Vascular , Rigidez Vascular , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Adulto , Estudios de Casos y Controles , Calcificación Vascular/sangre , Calcificación Vascular/fisiopatología , Calcificación Vascular/etiología , Calcificación Vascular/diagnóstico , Factores de Tiempo , Mediadores de Inflamación/sangre , Factores de Riesgo , Factores de Crecimiento de Fibroblastos/sangre , Factor-23 de Crecimiento de Fibroblastos , Quimiocina CCL2/sangre , Uremia/sangre , Uremia/diagnóstico , Uremia/fisiopatología , Indicán/sangre , Resultado del Tratamiento , Donadores VivosRESUMEN
OBJECTIVE: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample. DESIGN: Cross-sectional study. SETTING: Community-dwelling cohort. PARTICIPANTS: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing. RESULTS: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance. CONCLUSION: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS.
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Dolor Crónico , Síndromes de Ojo Seco , Síndrome del Colon Irritable , Humanos , Estudios Transversales , Masculino , Femenino , Dolor Crónico/diagnóstico , Persona de Mediana Edad , Síndrome del Colon Irritable/diagnóstico , Adulto , Síndromes de Ojo Seco/diagnóstico , Anciano , Biomarcadores/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Factor de Necrosis Tumoral alfa/sangre , Quimiocina CCL2/sangre , Reino Unido/epidemiología , Interleucina-10/sangre , Dimensión del Dolor/métodosRESUMEN
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.
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Biomarcadores , Enfermedades de las Arterias Carótidas , Grosor Intima-Media Carotídeo , Citocinas , Inflamación , Humanos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Enfermedades de las Arterias Carótidas/sangre , Citocinas/sangre , Inflamación/sangre , Factores de Riesgo , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Arterias Carótidas/patología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Quimiocina CCL2/sangre , Mediadores de Inflamación/sangre , Enfermedades AsintomáticasRESUMEN
OBJECTIVE: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children. METHODS: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years. We examined associations of microbial taxa and metabolites-examining microbe-dependent and non-microbe-dependent metabolites separately-with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker. RESULTS: Of 335 taxa tested, 149 were associated (qFDR<0.05) with at least one inflammatory marker; 10 of these were robust to pseudocount choice. Several bacterial taxa involved in tryptophan metabolism were associated with inflammation, including kynurenine-degrading Ruminococcus, which was inversely associated with all inflammation markers. Of 1037 metabolites tested, 315 were previously identified as microbe dependent and were more frequently associated with PAI-1 and the InfSc than non-microbe dependent metabolites. In total, 87 metabolites were associated (qFDR<0.05) with at least one inflammation marker, including kynurenine (positively), serotonin (positively), and tryptophan (inversely). CONCLUSION: A distinct set of gut microbes and microbe-dependent metabolites, including those involved in the tryptophan-kynurenine-serotonin pathway, may be implicated in inflammatory pathways in childhood.
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Biomarcadores , Microbioma Gastrointestinal , Inflamación , Metaboloma , Inhibidor 1 de Activador Plasminogénico , Humanos , Microbioma Gastrointestinal/fisiología , Niño , Femenino , Masculino , Inflamación/microbiología , Inflamación/sangre , Biomarcadores/sangre , Estudios Prospectivos , Preescolar , Inhibidor 1 de Activador Plasminogénico/sangre , Metaboloma/fisiología , Triptófano/sangre , Triptófano/metabolismo , Quinurenina/sangre , Quinurenina/metabolismo , Factor de Necrosis Tumoral alfa/sangre , ARN Ribosómico 16S/genética , Quimiocina CCL2/sangreRESUMEN
BACKGROUND: Renal disease in canine leishmaniosis is of great importance owing to increased risk of mortality. In human visceral leishmaniosis, monocyte chemoattractant protein-1 (MCP-1) has been used as a marker of renal damage and inflammation. The purpose of this study was first to determine the serum MCP-1 and urinary MCP-1-to-creatinine ratio (uMCP-1/Cr) in healthy dogs and dogs with leishmaniosis at diagnosis, and second to determine whether these markers can differentiate disease severity at diagnosis. METHODS: In total, 19 healthy seronegative dogs and 38 dogs with leishmaniosis were included in the study. Dogs with leishmaniosis were classified as LeishVet clinical staging and as International Renal Interest Society (IRIS) staging. Serum and urinary MCP-1 concentrations were measured with an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve determined disease severity at diagnosis between two LeishVet groups (Stage II versus stage III and IV). RESULTS: Dogs in Leishvet stages IIb, III, and IV had a median serum MCP-1 and uMCP-1/Cr concentration higher than healthy dogs (P < 0.0001). No statistical differences were found in serum MCP-1 and uMCP-1/Cr between dogs in LeishVet stage IIa and healthy dogs. The dogs in LeishVet stage IV had significantly higher serum MCP-1 and uMCP-1/Cr compared with the dogs in LeishVet stage IIa (P < 0.0001). Serum MCP-1 and uMCP-1 were significantly higher in dogs in IRIS stage I and II + III + IV compared with healthy dogs. Dogs stage II + III + IV of IRIS had a significantly higher serum MCP-1 compared with dogs in IRIS stage I (P < 0.0001). The area under the ROC curve for serum MCP-1 was 0.78 [95% confidence interval (CI) 0.64-0.93] and for uMCP-1/Cr it was 0.86 (95% CI, 0.74-0.99). The optimal cutoff value for serum MCP-1 and uMCP-1/Cr was 336.85 pg/ml (sensitivity of 79% and specificity of 68%) and 6.89 × 10-7 (sensitivity of 84% and specificity of 79%), respectively. CONCLUSIONS: Serum MCP-1 and uMCP-1/Cr are increased in dogs with leishmaniosis compared with healthy dogs, suggesting the presence of inflammation and renal injury. Serum MCP-1 and uMCP-1/Cr were more elevated in the advanced stages of the disease compared with the moderate stages and, therefore, can be markers of the severity of the disease process.
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Biomarcadores , Quimiocina CCL2 , Enfermedades de los Perros , Inflamación , Leishmaniasis , Animales , Perros , Quimiocina CCL2/sangre , Quimiocina CCL2/orina , Enfermedades de los Perros/orina , Enfermedades de los Perros/sangre , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/parasitología , Biomarcadores/sangre , Biomarcadores/orina , Leishmaniasis/veterinaria , Leishmaniasis/sangre , Leishmaniasis/orina , Leishmaniasis/diagnóstico , Leishmaniasis/patología , Masculino , Inflamación/veterinaria , Inflamación/sangre , Inflamación/orina , Femenino , Enfermedades Renales/veterinaria , Enfermedades Renales/sangre , Enfermedades Renales/orina , Enfermedades Renales/patología , Enfermedades Renales/diagnóstico , Enfermedades Renales/parasitología , Curva ROC , Creatinina/sangre , Creatinina/orina , Ensayo de Inmunoadsorción Enzimática/veterinaria , Índice de Severidad de la EnfermedadRESUMEN
Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.
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Fragilidad , Inflamación , Desnutrición , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Anciano , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre , Desnutrición/sangre , Fragilidad/sangre , Fragilidad/complicaciones , Inflamación/sangre , Estudios Transversales , Anciano de 80 o más Años , Anciano Frágil , Citocinas/sangre , Tasa de Filtración Glomerular , Evaluación Geriátrica/métodos , Interleucina-6/sangre , Síndrome , Quimiocina CCL2/sangreRESUMEN
BACKGROUND: Recent Mendelian randomization and meta-analysis highlight the relevance of MCP-1 (monocyte chemoattractant protein-1) in stroke. We aimed to investigate the associations between MCP-1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships. METHODS AND RESULTS: A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all-cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP-1 level (<337.6 pg/mL) was associated with a reduced risk of all-cause death (hazard ratio [HR], 0.65 [95% CI, 0.51-0.82]) and poor functional outcome (odds ratio, 0.81 [95% CI, 0.70-0.94]) but was not associated with recurrent stroke (HR, 1.10 [95% CI, 0.95-1.27]), compared with high MCP-1 level (≥337.6 pg/mL). The association between MCP-1 and all-cause death was partially mediated by highly sensitive C-reactive protein, interleukin-6, and YKL-40 (Chitinase-3-like protein 1; mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9%, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP-1 and inflammatory biomarkers had the highest risks of all-cause death and poor functional outcome. CONCLUSIONS: Low plasma MCP-1 level was associated with decreased risks of all-cause mortality and poor functional outcome after ischemic stroke or transient ischemic attack. Inflammation partially mediated and jointly contributed to the associations.
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Biomarcadores , Quimiocina CCL2 , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Sistema de Registros , Humanos , Masculino , Quimiocina CCL2/sangre , Femenino , Biomarcadores/sangre , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/mortalidad , Ataque Isquémico Transitorio/diagnóstico , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Persona de Mediana Edad , Anciano , Pronóstico , China/epidemiología , Inflamación/sangre , Recurrencia , Medición de Riesgo , Factores de Riesgo , Causas de MuerteRESUMEN
BACKGROUND: Anterior cruciate ligament injury and anterior cruciate ligament reconstruction (ACLR) are risk factors for symptomatic posttraumatic osteoarthritis (PTOA). After ACLR, individuals demonstrate altered joint tissue metabolism indicative of increased inflammation and cartilage breakdown. Serum biomarker changes have been associated with tibiofemoral cartilage composition indicative of worse knee joint health but not with PTOA-related symptoms. PURPOSE/HYPOTHESIS: The purpose of this study was to determine associations between changes in serum biomarker profiles from the preoperative sample collection to 6 months after ACLR and clinically relevant knee PTOA symptoms at 12 months after ACLR. It was hypothesized that increases in biomarkers of inflammation, cartilage metabolism, and cartilage degradation would be associated with clinically relevant PTOA symptoms after ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Individuals undergoing primary ACLR were included (N = 30). Serum samples collected preoperatively and 6 months after ACLR were processed to measure markers indicative of changes in inflammation (ie, monocyte chemoattract protein 1 [MCP-1]) and cartilage breakdown (ie, cartilage oligomeric matrix protein [COMP], matrix metalloproteinase 3, ratio of type II collagen breakdown to type II collagen synthesis). Knee injury and Osteoarthritis Outcome Score surveys were completed at 12 months after ACLR and used to identify participants with and without clinically relevant PTOA-related symptoms. K-means cluster analyses were used to determine serum biomarker profiles. One-way analyses of variance and logistic regressions were used to assess differences in Knee injury and Osteoarthritis Outcome Score subscale scores and clinically relevant PTOA-related symptoms between biomarker profiles. RESULTS: Two profiles were identified and characterized based on decreases (profile 1: 67% female; age, 21.4 ± 5.1 years; body mass index, 24.4 ± 2.4) and increases (profile 2: 33% female; age, 21.3 ± 3.2 years; body mass index, 23.4 ± 2.6) in sMCP-1 and sCOMP preoperatively to 6 months after ACLR. Participants with profile 2 did not demonstrate differences in knee pain, symptoms, activities of daily living, sports function, or quality of life at 12 months after ACLR compared to those with profile 1 (P = .56-.81; η2 = 0.002-0.012). No statistically significant associations were noted between biomarker profiles and clinically relevant PTOA-related symptoms (odds ratio, 1.30; 95% CI, 0.23-6.33). CONCLUSION: Serum biomarker changes in MCP-1 and sCOMP within the first 6 months after ACLR were not associated with clinically relevant PTOA-related symptoms.
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Reconstrucción del Ligamento Cruzado Anterior , Biomarcadores , Cartílago Articular , Osteoartritis de la Rodilla , Humanos , Biomarcadores/sangre , Femenino , Masculino , Estudios de Casos y Controles , Adulto , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangre , Cartílago Articular/metabolismo , Adulto Joven , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicaciones , Lesiones del Ligamento Cruzado Anterior/sangre , Proteína de la Matriz Oligomérica del Cartílago/sangre , Quimiocina CCL2/sangre , Inflamación/sangre , Metaloproteinasa 3 de la Matriz/sangre , Articulación de la Rodilla/cirugía , Adolescente , Traumatismos de la Rodilla/cirugía , Traumatismos de la Rodilla/sangre , Traumatismos de la Rodilla/complicaciones , Colágeno Tipo II/sangreRESUMEN
INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed.METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry.RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently.DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages.Connolly DM, Madden LA, Edwards VC, Lee VM. Brain and lung biomarker responses to hyperoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(9):667-674.
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Biomarcadores , Quimiocina CCL2 , Receptor para Productos Finales de Glicación Avanzada , Humanos , Masculino , Biomarcadores/sangre , Biomarcadores/metabolismo , Adulto , Persona de Mediana Edad , Quimiocina CCL2/sangre , Receptor para Productos Finales de Glicación Avanzada/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Descompresión/métodos , Adulto Joven , Encéfalo/metabolismo , Pulmón , Enfermedad de Descompresión/sangre , Hiperoxia/sangreRESUMEN
It is not clear whether immunoregulatory cytokines and cells are associated with Disease Activity Score 28 (DAS28) scores and ultrasound grades/scores. Here, we investigated the relationships between immunoregulatory cytokines or cells and different DAS28 scores or ultrasound grades/scores in patients with rheumatoid arthritis (RA). This study enrolled 50 RA patients (with 147 visits) who had remission/low/moderate DAS28-ESR scores (92% in remission and low disease activity) at baseline. Blood was collected and an ultrasound was performed three times in a year. Percentages of regulatory B cells and T regulatory type 1 cells and M2 macrophage numbers in the blood were examined. Plasma levels of 10 immunoregulatory cytokines IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-35, TGF-ß1, sTNF-R1, and sTNF-R2 and monocyte chemotactic protein-1 (MCP-1) were assessed using ELISA assay. The correlations of cytokines and cells with different DAS28 scores and ultrasound grades were investigated, and cytokines and cells were compared between different categories of DAS28 scores and ultrasound grades. Plasma TGF-ß1 levels were higher in the DAS28-ESR < 2.6 (remission) subgroup than in the DAS28-ESR ≥ 2.6 (nonremission) subgroup (p = 0.037). However, plasma TGF-ß1 levels were higher in the high ultrasound grade subgroup than those in the low ultrasound grade subgroup (p = 0.007). The number of M2 macrophages was lower in the DAS28-MCP-1 < 2.2 subgroup than in the DAS28-MCP-1 ≥ 2.2 subgroup (p = 0.036). The levels of TGF-ß1, sTNF-R2, IL-10, and IL-27 were higher in patients with high ultrasound grades than in those with low ultrasound grades. IL-27 was also higher in the nonremission DAS28-ESR subgroup than the remission one (p = 0.025). Moreover, sTNF-R1 levels in the 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission subgroup were significantly lower than in the 2011 ACR/EULAR nonremission subgroup (p = 0.007). This trend was reflected in that lower sTNF-R1 levels correlated with low DAS28-MCP-1 scores (rho = 0.222, p = 0.007). We conclude that high plasma TGF-ß1 levels indicate the DAS28-ESR remission (<2.6) subgroup and the high ultrasound grade subgroup. IL-27 probably connects the nonremission DAS28-ESR to high ultrasound grades. Low sTNF-R1 levels probably link low DAS28-MCP-1 scores with the 2011 ACR/EULAR remission subgroup. It suggests that incongruent immuno-inflammatory abnormalities exist between DAS28 scores and ultrasound grades, and are also dissimilar among various DAS28-formula categories. Therefore, this study may provide a basis for further research into individual cytokines and immunoregulatory cells behind each DAS28 formula and ultrasound grades/scores.
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Artritis Reumatoide , Citocinas , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta1 , Ultrasonografía , Humanos , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Citocinas/sangre , Citocinas/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Anciano , Adulto , Interleucinas/sangre , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Interleucina-27/sangre , Interleucina-10/sangre , Inducción de Remisión , Interleucina-9/sangre , Quimiocina CCL2/sangreRESUMEN
OBJECTIVE: This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis. METHODS: This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis. RESULTS: After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up. CONCLUSION: These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.
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Biomarcadores , Inflamación , Diálisis Peritoneal , Humanos , Diálisis Peritoneal/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios Prospectivos , Inflamación/sangre , Inflamación/mortalidad , Anciano , Estimación de Kaplan-Meier , Ensayo de Inmunoadsorción Enzimática , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Adulto , Citocinas/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/análisis , Quimiocina CCL2/sangre , Quimiocina CCL2/análisis , Diálisis Renal/mortalidad , Factores de Riesgo , Interleucina-17/sangre , Causas de Muerte , Citometría de FlujoRESUMEN
BACKGROUND: Previous observational studies have reported the correlation between circulating inflammatory cytokines and cerebral small vessel disease (CSVD). However, the causality of this association is uncertain. This study used Mendelian randomization to investigate the causal effect of circulating inflammatory cytokines on neuroimaging changes in CSVD. METHODS: This study utilized genetic variances of 41 inflammatory cytokines and 3 neuroimaging markers of CSVD from genome-wide association studies to assess the causal effects in a two-sample Mendelian randomization approach. Inverse variance weighted analysis was used as the main analytical method, and sensitivity analysis was used to further validate the robustness of the results. RESULTS: Increased IL-18 was associated with increased white matter hyperintensity (WMH) and mean diffusivity (MD) (ß = 0.034, 95 % CI 0.002, 0.065, P=0.038, ß = 0.157, 95 % CI 0.015, 0.299, P=0.030). However, increased IL-18 was associated with decreased fractional anisotropy (FA) (ß = -0.141, 95 % CI -0.279, -0.002, P=0.047). Increased monocyte chemotactic protein-1(MCP-1) was associated with decreased FA (ß = -0.278, 95 % CI -0.502, -0.054, P=0.015). Increased IL-10 levels and IL-2ra levels were associated with decreased risks of MD (ß = -0.228, 95 % CI -0.448, -0.009, p = 0.041; ß = -0.204, 95 % CI=-0.377, -0.031, p = 0.021). CONCLUSIONS: This study revealed that increased levels of IL-18 and MCP-1 were associated with white matter microstructural injury, and increased levels of IL-10 and IL-2ra were associated with decreased MD.
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Enfermedades de los Pequeños Vasos Cerebrales , Citocinas , Estudio de Asociación del Genoma Completo , Interleucina-18 , Imagen por Resonancia Magnética , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Citocinas/sangre , Imagen por Resonancia Magnética/métodos , Interleucina-18/sangre , Interleucina-18/genética , Sustancia Blanca/diagnóstico por imagen , Biomarcadores/sangre , Masculino , Femenino , Quimiocina CCL2/sangre , Quimiocina CCL2/genéticaRESUMEN
Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age.
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Envejecimiento , Enterococcus faecalis , Hígado , Animales , Hígado/metabolismo , Ratones , Masculino , Interleucina-10/sangre , Interleucina-10/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/sangre , Probióticos/administración & dosificación , Ratones Endogámicos C57BL , Metabolismo de los LípidosRESUMEN
It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce.
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Biomarcadores , Diabetes Gestacional , Inflamación , Resultado del Embarazo , Embarazo Gemelar , Humanos , Femenino , Embarazo , Adulto , Embarazo Gemelar/sangre , Embarazo Gemelar/inmunología , Biomarcadores/sangre , Diabetes Gestacional/inmunología , Diabetes Gestacional/sangre , Inflamación/inmunología , Inflamación/sangre , Estilo de Vida , Preeclampsia/sangre , Preeclampsia/inmunología , Preeclampsia/epidemiología , Fumar/efectos adversos , Fumar/sangre , Interleucina-8/sangre , Proteína C-Reactiva/análisis , Quimiocina CCL2/sangre , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Índice de Masa Corporal , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/sangreRESUMEN
INTRODUCTION: Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. METHODS: Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. RESULTS: A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3ß, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. CONCLUSION: We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.
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COVID-19 , Quimiocina CX3CL1 , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-6 , Humanos , COVID-19/mortalidad , COVID-19/sangre , COVID-19/inmunología , Masculino , Femenino , Anciano , Proteína Antagonista del Receptor de Interleucina 1/sangre , Persona de Mediana Edad , Interleucina-6/sangre , Quimiocina CX3CL1/sangre , Interleucina-8/sangre , Quimiocina CCL2/sangre , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Citocinas/sangre , Anciano de 80 o más Años , Hospitalización , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/sangre , Respiración ArtificialRESUMEN
Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.
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Citocinas , Dieta Mediterránea , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/dietoterapia , Insuficiencia Cardíaca/terapia , Masculino , Femenino , Citocinas/sangre , Anciano , Persona de Mediana Edad , Ácidos Grasos Omega-3/administración & dosificación , Quimiocina CCL2/sangre , Apoyo Nutricional/métodos , Interleucina-6/sangre , Interleucina-8/sangre , Inflamación/sangreRESUMEN
Introduction: Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. Methods: We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Results: Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Conclusions: Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.
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Quimiocina CCL2 , Interleucina-8 , Mieloma Múltiple , Factor A de Crecimiento Endotelial Vascular , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factor A de Crecimiento Endotelial Vascular/sangre , Interleucina-8/sangre , Pronóstico , Quimiocina CCL2/sangre , Interleucina-6/sangre , Estudios Prospectivos , Adulto , Anciano de 80 o más Años , Citocinas/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Major depressive disorder (MDD) is a common and debilitating mental illness characterized by persistent feelings of sadness, hopelessness, and a lack of interest in daily activities. The objective of this study was to investigate whether levels of macrophage inflammatory protein-1ß (MIP-1ß) and macrophage chemoattractant protein-2 (MCP-2) in the blood were associated with the pathophysiology and development of MDD compared to healthy controls (HCs). METHODS: This case-control study was conducted involving 50 MDD patients and 38 HCs. We performed a comprehensive assessment to match age, sex, BMI, and socio-demographic profile between the groups. The study excluded participants with chronic infection, inflammatory diseases, coexisting psychiatric disorder, history of liver and kidney diseases, and individuals who are under antipsychotic medications. A professional psychiatrist diagnosed MDD patients and evaluated HCs based on the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria. The severity of depression was assessed using the Hamilton Depression (Ham-D) rating scale. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to quantify the serum MIP-1ß and MCP-2 levels. RESULTS: The results indicated elevated serum MIP-1ß levels (207.73±24.24 pg/ml) in MDD patients compared to HCs (58.77±9.14 pg/ml). This difference in concentration is positively correlated with severity of disease symptoms (r = 0.451; p<0.001). Similarly, the levels of MCP-2 were found to be elevated in patients compared to controls (143.61±19.92 vs. 56.84±4.02 pg/ml; p = 0.003), with a positive correlation with the Ham-D scores (r = 0.373; p = 0.004). CONCLUSION: According to this study, elevated levels of MIP-1ß and MCP-2 may be associated with the pathophysiology and development of MDD. These increased serum MIP-1ß and MCP-2 levels could be used as risk assessment tools for MDD. The present findings urge further research and the development of therapeutic and diagnostic approaches for depression.
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Quimiocina CCL2 , Quimiocina CCL4 , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/diagnóstico , Masculino , Femenino , Estudios de Casos y Controles , Adulto , Quimiocina CCL4/sangre , Quimiocina CCL2/sangre , Persona de Mediana Edad , Biomarcadores/sangreRESUMEN
There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.
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Citocinas , Inflamación , Neoplasias , Apoyo Nutricional , Proteína de Suero de Leche , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Inflamación/sangre , Apoyo Nutricional/métodos , Citocinas/sangre , Adulto , Suplementos Dietéticos , Quimiocina CCL2/sangreRESUMEN
PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.