RESUMEN
Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients.
Asunto(s)
Envejecimiento/inmunología , Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto , Factores de Edad , Envejecimiento/patología , Anticuerpos Antivirales/biosíntesis , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Estudios de Casos y Controles , Femenino , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Interleucina-10/biosíntesis , Interleucina-10/inmunología , Interleucina-17/biosíntesis , Interleucina-17/inmunología , Interleucinas/biosíntesis , Interleucinas/inmunología , Masculino , Persona de Mediana Edad , Péptidos/farmacología , Cultivo Primario de Células , Toxoide Tetánico/farmacología , Carga Viral/efectos de los fármacos , Proteínas Virales/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
Interleukin-6 (IL-6) has been implicated in the induction of pathogenic IL-17-producing T cells in autoimmune diseases, and studies evaluating the role of this cytokine in T-cell function in patients with multiple sclerosis (MS) are lacking. Our objective was to evaluate the role of IL-6 receptor (IL-6R) signalling on in vitro functional status of T cells from patients with relapsing-remitting MS during clinical remission. Our results demonstrated that, even during the remission phase, activated T cells from patients produce higher levels of IL-17, and this cytokine was positively correlated with disease severity, as determined by Expanded Disability Status Scale score. In the MS group, the blockade of IL-6R signalling by anti-IL-6R monoclonal antibody reduced IL-17 production and elevated IL-10 release by activated CD4(+) T cells, but it did not alter the production of these cytokines by activated CD8(+) T cells. Blockade of IL-6R signalling also reduced the ability of monocytes to up-regulate T helper type 17 phenotype in patients with MS. Finally, both cell proliferation and IL-17 release by CD4(+) and, mainly, CD8(+) T cells from patients with MS were less sensitive to hydrocortisone inhibition than control group. Interestingly, IL-6R signalling blockade restored the ability of hydrocortisone to inhibit both T-cell proliferation and IL-17 production. Collectively, these results suggest that IL-6 might be involved in MS pathogenesis by enhancing IL-17 production and reducing corticoid inhibitory effects on activated T cells.
Asunto(s)
Interleucina-17/biosíntesis , Interleucina-6/metabolismo , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Corticoesteroides/metabolismo , Corticoesteroides/farmacología , Adulto , Citocinas/biosíntesis , Resistencia a Medicamentos , Femenino , Humanos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Receptores de Interleucina-6/metabolismo , Transducción de Señal , Subgrupos de Linfocitos T/efectos de los fármacos , Células Th17/inmunología , Células Th17/metabolismo , Adulto JovenRESUMEN
Dopamine (DA) is a neurotransmitter produced mainly in the central nervous system (CNS) that has immunomodulatory actions on T cells. As the multiple sclerosis (MS) has long been regarded as an autoimmune disease of CNS mediated by T cells, the objective of this study was to evaluate the impact of DA on in vitro functional status of T cells from relapsing-remitting (RR)-MS patients. Peripheral T-cells from RR-MS patients were activated by mitogens and cell proliferation and cytokine production were assayed by [(3)H]-thymidine uptake and ELISA, respectively. Our results demonstrated that DA enhanced in vitro T cell proliferation and Th17-related cytokines in MS-derived cell cultures. In addition, this catecholamine reduced Treg-related cytokines (IL-10 and TGF-ß) release by activated CD4(+) T cells. These DA-induced effects on T cells were mainly dependent on IL-6 production by both polyclonally-activated CD4(+) T cells and LPS-stimulated monocytes. Furthermore, the production of IL-17 and IL-6 by MS-derived T cells was directly related with neurological disability (EDSS score), and the release of these cytokines was less sensitive to glucocorticoid inhibition in MS patients than in control group, mainly after DA addition. In conclusion, our data suggest that DA amplifies glucocorticoid-resistant Th17 phenotype in MS patients, and this phenomenon could be, at least in part, due to its ability to induce IL-6 production by monocytes and CD4(+) T cells.
Asunto(s)
Dopamina/farmacología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Neuroinmunomodulación/fisiología , Células Th17/inmunología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , División Celular , Células Cultivadas , Resistencia a Medicamentos , Femenino , Humanos , Interleucina-10/biosíntesis , Interleucina-10/genética , Interleucina-6/biosíntesis , Interleucina-6/genética , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Fitohemaglutininas/farmacología , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Adulto JovenRESUMEN
The number of HIV-infected young women has been increasing since the beginning of the AIDS epidemic. The objective of the present study was to investigate the impact of anti-retroviral treatment (ART) of HIV-1-infected pregnant women (PW) on cytokine profile of uninfected neonates. Our results demonstrated that higher levels of IL-1ß and TNF-α associated with lower IL-10 production were detected in the plasma obtained from neonates born from ART-treated PW. Furthermore, the production of TNF- α and IFN-γ was also significantly higher in polyclonally-activated T cells from those neonates. This elevated pro-inflammatory pattern detected by these activated-T cells was not associated to HIV-1 antigens sensitization. Finally, ART-exposed neonates showed to be born with lower weight, and it was inversely correlated with maternal peripheral TNF-a level. In summary, the data presented here suggest a significant disturbance in cytokine network of HIV-1-uninfected neonates exposed to potent anti-retroviral schemes during pregnancy.
Asunto(s)
Citocinas/inmunología , Infecciones por VIH/tratamiento farmacológico , VIH/inmunología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Linfocitos T/inmunología , Adulto , Antígenos Virales/inmunología , Terapia Antirretroviral Altamente Activa/efectos adversos , Peso Corporal/efectos de los fármacos , Células Cultivadas , Femenino , Infecciones por VIH/inmunología , Humanos , Inmunidad Materno-Adquirida/efectos de los fármacos , Recién Nacido , Activación de Linfocitos/efectos de los fármacos , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Adulto JovenRESUMEN
The pathogenesis of neuromyelitis optica (NMO) is influenced by a combination of genetic and environmental factors, including infectious agents. Several infectious diseases can both trigger or exacerbate autoimmunity. The objective of the present work was to evaluate the in vitro immune responsiveness to Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA) in remittent-recurrent NMO patients, and correlate it with the level of neurological disability. Our results revealed that the extent of lymphoproliferation and cytokine profile in response to SA- and CA-stimulated PBMC cultures was similar between NMO patients and healthy individuals. Nevertheless, a higher in vitro CD4(+) T cell proliferation associated with elevated IL-1ß, IL-6 and IL-17 release was observed in NMO-derived EC-stimulated cell cultures. Additionally, in these last cultures, the IL-10 production was significantly lower as compared with control group. The in vitro EC-induced levels of IL-6 and IL-17 were positively related with neurological disabilities. This higher tendency to produce Th17-related cytokines was proportional to the production of IL-23 and IL-6 by LPS-activated monocytes. Interestingly, elevated LPS levels were quantified in the plasma of NMO patients. The results suggest that a higher Th17-responsiveness to E. coli could be involved in the NMO pathogenesis.
Asunto(s)
Candida albicans/inmunología , Escherichia coli/inmunología , Neuromielitis Óptica/inmunología , Staphylococcus aureus/inmunología , Células Th17/inmunología , Adulto , Antígenos Bacterianos/inmunología , Proliferación Celular , Células Cultivadas , Citocinas/metabolismo , Femenino , Humanos , Inmunidad Celular , Lipopolisacáridos/sangre , Lipopolisacáridos/inmunología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/microbiología , Neuromielitis Óptica/fisiopatología , Adulto JovenRESUMEN
Exogenous glucocorticoid plays an important role in controlling clinical relapses of multiple sclerosis (MS), but the response to this treatment differs among patients. In this study, T-cell proliferation and IL-17 production were less sensitive to hydrocortisone (HC) inhibition in MS patients than healthy individuals, mainly in CD8(+) compartment. Furthermore, in vitro IL-17 production was positively related with neurological disability and its release was proportional to IL-23 and IL-6 productions by LPS-activated monocytes. Interestingly, elevated LPS levels were quantified in the plasma of MS patients, and their levels were directly related to in vivo IL-6 production. Finally, HC-resistance in reducing IL-17 production by polyclonally-activated CD8(+) T cells was particularly observed among MS patients with higher in vivo LPS levels. In summary, the results indicate that T-cells derived from MS patients show an enhanced Th17-like phenotype that is directly associated with neurological disability, resistance to glucocorticoid inhibition and elevated bacterial translocation.
Asunto(s)
Citocinas/metabolismo , Glucocorticoides/farmacología , Lipopolisacáridos/sangre , Esclerosis Múltiple/inmunología , Células Th17/fisiología , Adulto , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/antagonistas & inhibidores , Citocinas/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hidrocortisona/farmacología , Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/inmunología , Esclerosis Múltiple/metabolismo , Células Th17/efectos de los fármacos , Adulto JovenRESUMEN
Neuromyelitis optica (NMO), also known as Devic's disease, is an autoimmune, inflammatory disorder of the central nervous system (CNS) in which the immune system attacks myelin of the neurons located at the optic nerves and spinal cord, thus producing a simultaneous or sequential optic neuritis and myelitis. The objective of this study was evaluated the background T-cell function of patients suffering from neuromyelitis optica (NMO), an autoimmune disorder of the central nervous system. In our study, the in vitro T cell proliferation and the production of Th1 cytokines were significantly lower in cell cultures from NMO patients, as compared with healthy individuals. In contrast, a dominant Th17-like phenotype, associate with higher IL-23 and IL-6 production by LPS-activated monocytes, was observed among NMO patients. The release of IL-21 and IL-6 by polyclonally activated CD4+ T cells was directly correlated to neurological disability. In addition, the in vitro release of IL-21, IL-6 and IL-17 was significantly more resistant to glucocorticoid inhibition in NMO patients. In conclusion, the results indicate dominant Th17-related response in NMO patients that was directly proportional to neurological disability. Furthermore, our results can help to explain why NMO patients trend to be more refractory to corticoid treatment.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Interleucina-6/biosíntesis , Interleucinas/biosíntesis , Activación de Linfocitos/inmunología , Neuromielitis Óptica/inmunología , Adulto , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Células Cultivadas , Femenino , Humanos , Interleucina-6/metabolismo , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/metabolismo , Neuromielitis Óptica/fisiopatologíaRESUMEN
Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , VIH-1/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Antígenos VIH/administración & dosificación , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Técnicas In Vitro , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Interleucina-10/biosíntesis , Activación de Linfocitos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Subgrupos de Linfocitos T/virología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/virología , Replicación Viral/inmunología , Adulto JovenRESUMEN
This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1ß by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , VIH-1/efectos de los fármacos , Interleucina-10/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Factores de Edad , Anticuerpos Monoclonales/farmacología , Terapia Antirretroviral Altamente Activa , Antivirales/administración & dosificación , Células Cultivadas , Femenino , VIH-1/fisiología , Humanos , Memoria Inmunológica , Inmunofenotipificación , Interleucina-10/antagonistas & inhibidores , Interleucina-1beta/biosíntesis , Interleucina-1beta/inmunología , Interleucina-6/biosíntesis , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/patología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/patología , Replicación Viral/efectos de los fármacosRESUMEN
Our objective was to evaluate the effect of stress-related dose of dopamine (DA) on the in vitro proliferation and cytokine production in polyclonally-activated T cells from healthy individuals or individuals with generalized anxiety disorder (GAD). Our results demonstrated that cell cultures from GAD group proliferated less following T cell activation, as compared with control group. The addition of DA reduced the proliferative response in cell cultures from healthy but not from GAD individuals. The cytokine profile in GAD individuals revealed Th1 and Th2 deficiencies associated with a dominant Th17 phenotype, which was enhanced by DA. A similar DA-induced immunomodulation was also observed in PPD-activated cell cultures from GAD individuals. Unlike the control, DA-enhanced Th17 cytokine production in GAD individuals was not affected by glucocorticoid. In conclusion, our results show that the T cell functional dysregulation in GAD individuals is significantly amplified by DA. These immune abnormalities can have impact in increasing the susceptibility of individuals with anxiety disorders to infectious diseases and inflammatory/autoimmune disorders.
Asunto(s)
Trastornos de Ansiedad/patología , Citocinas/metabolismo , Dopamina/farmacología , Células Th17/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Adolescente , Adulto , Antígenos CD/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Citometría de Flujo , Glucocorticoides/metabolismo , Humanos , Masculino , Mitógenos/farmacología , Fenotipo , Fitohemaglutininas/farmacología , Timidina/metabolismo , Tritio/metabolismo , Tuberculina/farmacología , Adulto JovenRESUMEN
Our objective was to evaluate the effect of stress-related dose of substance P (SP) on the in vitro proliferation and cytokine production in polyclonally activated T cells from healthy individuals or individuals with generalized anxiety disorder (GAD). Our results demonstrated that cell cultures from GAD group proliferated less following T cell activation, as compared with control group. The addition of SP enhanced, while the glucocorticoid (GC) reduced, the proliferative response in activated cell cultures from healthy but not from GAD individuals. The cytokine profile in GAD individuals revealed Th1 and Th2 deficiencies were associated with dominate Th17 phenotype which was enhanced by SP. Differently from control, the production of Th17 cytokines in GAD individuals was not affected by GC. In conclusion, our results show that complex T cell functional dysregulation in GAD individuals is significantly amplified by SP. These immune abnormalities can have impact in increasing the susceptibility to infectious diseases and inflammatory/autoimmune disorders in anxious individuals.
Asunto(s)
Trastornos de Ansiedad/inmunología , Resistencia a Medicamentos , Glucocorticoides/farmacología , Activación de Linfocitos/efectos de los fármacos , Sustancia P/inmunología , Linfocitos T/efectos de los fármacos , Células Th17/inmunología , Adolescente , Adulto , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/fisiopatología , Células Cultivadas , Femenino , Humanos , Masculino , Fenotipo , Sustancia P/farmacología , Linfocitos T/inmunología , Células Th17/efectos de los fármacos , Adulto JovenRESUMEN
The generalized anxiety disorder (GAD) is often a debilitating chronic condition, characterized by long-lasting anxiety that is not focused on any object or situation. Besides being clearly linked to increased susceptibility to infectious diseases, anxiety is also known to contribute to the pathogenesis of many inflammatory/autoimmune disorders. The present work aimed to explore the T cell profile following in vitro activation in cultures obtained from a group of individuals with GAD, comparing them with healthy control individuals. Our results demonstrated that cell cultures from GAD group proliferated less following T cell activation as compared with the control group. The analysis of the cytokine profile revealed Th1 and Th2 cytokine deficiencies in the anxious group, as compared with the control subjects. On the other hand, this cellular and humoral immune damage was followed by enhanced production of Th17-derived cytokines. In particular, the levels of TNF-α and IL-17 were significantly higher in cell cultures containing activated T cells from GAD individuals. Therefore, besides a deficiency on Th1 phenotype, an elevated proinflammatory status of these individuals might be related to both glucocorticoid immune resistance and lower IL-10 levels produced by activated T cells. In conclusion, our results demonstrated a T cell functional dysregulation in individuals with GAD, and can help to explain the mechanisms of immune impairment in these subjects and their relationship with increased susceptibility to infections and autoimmune diseases.
Asunto(s)
Trastornos de Ansiedad/patología , Fenotipo , Células Th17/inmunología , Células Th17/patología , Adolescente , Adulto , Trastornos de Ansiedad/sangre , Trastornos de Ansiedad/fisiopatología , Recuento de Células/métodos , Citocinas/metabolismo , Dexametasona/farmacología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Glucocorticoides/farmacología , Humanos , Interleucina-7/farmacología , Activación de Linfocitos/inmunología , Masculino , Estadísticas no Paramétricas , Sales de Tetrazolio , Células Th17/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Adulto JovenRESUMEN
The purpose of this study was to evaluate the impact of age on tetanus-specific immune response in successfully highly active antiretroviral therapy-treated AIDS patients, using healthy age-matched individuals as controls. Whole Peripheral blood mononuclear cells or CD8(+) cell-depleted peripheral blood mononuclear cells from previously tetanus toxoid (TT)-immunized individuals were activated with TT plus IL-2, and cell proliferation, cytokine production, and in vitro HIV-1 replication were measured. The in vivo magnitude of the humoral immune response was also assessed by antibody measurements. Our results showed that, compared with other groups, both in vitro TT-specific lymphoproliferation and serum antibody concentration were lower in older AIDS patients. Although the IL-1beta and tumour necrosis factor alpha (TNF-alpha) production were higher in cultures from aged HIV-1-infected patients, a dramatic damage on the interferon gamma (IFN-gamma) release was observed, when compared with younger patients. CD8(+) T lymphocytes depletion reduced IL-1beta and TNF-alpha release in the older groups, however, it did not significantly alter their IFN-gamma production. Furthermore, the neutralization of endogenous IL-10 did not change the IFN-gamma deficiency in older AIDS patients. Finally, the lower cellular immune response in this patient group was not related to in vitro HIV-1 replication. The results suggest that successfully highly active antiretroviral therapy-treated aged AIDS patients do not reconstitute the immune response to TT, making them probably more susceptible to tetanus even after vaccination.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Toxoide Tetánico/inmunología , Adulto , Factores de Edad , Anciano , Anticuerpos Antibacterianos/sangre , Proliferación Celular , Citocinas/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Intestinal barrier disruption followed by bacterial translocation seems to play a role in secondary pancreatic infection in acute pancreatitis. The use of probiotics as a possible adjuvant strategy in the treatment of acute pancreatitis needs to be investigated. OBJECTIVE: The aim of this study was to determine the effects of dietary supplementation with a prophylactically administered multispecies probiotic mixture on the markers of acute pancreatitis and on the occurrence of bacterial translocation. METHODS: Thirty adult male Wistar rats were randomly assigned to 1 of 3 groups of 10 rats each: (1) the PS group, in which the rats were given probiotic supplementation prior to induction of acute pancreatitis; (2) the WP group, in which the rats underwent surgery to induce acute pancreatitis without prior probiotic supplementation; and (3) the control group, in which the rats underwent sham surgery. For 14 days before surgery, animals in the PS group received a single daily dose containing ~1.2 × 10(9) colony-forming units of a probiotic mixture administered intragastrically as a bolus. On day 15, the animals underwent surgery to induce acute pancreatitis (PS and WP groups) or simulated surgery (control group). Blood samples were collected to determine leukocyte count, amylase and lipase activities, and glucose and calcium concentrations immediately before and 6 and 12 hours after the beginning of the procedure. Samples of pancreas, spleen, liver, and mesenteric lymph nodes were harvested for microbiologic and histopathologic analysis after the last blood sample collection. The pathologist examining the histopathology was blinded to treatment assignment. RESULTS: The mean leukocyte count was significantly increased in the PS group compared with the WP group (P = 0.018), whereas the serum amylase and lipase activities and the serum glucose and calcium concentrations were not significantly different between the 2 groups. Comparing the risk for tissue colonization in the PS group with that of the WP group, the odds ratio (OR) for pancreas was 2.91 (95% CI, 0.13-67.10); liver, 66.55 (95% CI, 1.89-2282.66); spleen, 88.58 (95% CI, 3.04-2583.08); and mesenteric lymph nodes, 1.23 (95% CI, 0.06-25.48). When the risks for histopathologic changes were compared between the 2 groups, the OR for acinar necrosis was 1.73 (95% CI, 0.21-12.17); steatonecrosis, 12.08 (95% CI, 1.26-115.54); hemorrhage, 1.38 (95% CI, 0.21-9.53); and leukocyte infiltration, 5.91 (95% CI, 0.64-54.89). CONCLUSION: Probiotic supplementation before the induction of acute pancreatitis was associated with a greater degree of bacterial translocation and pancreatic tissue damage in this animal model.
RESUMEN
OBJECTIVE: This study aimed to evaluate the impact of pregnancy-related immune events on the HIV-1 replication and to analyze their relationship with the risk of vertical transmission. METHODS: The peripheral blood from HIV-1-infected pregnant women who controlled (G1) or not controlled (G2) their plasma viral load was drawn, and the plasma and the T cells were obtained. The T-cell cultures were activated in vitro with anti-CD3 and anti-CD28, and the proliferation and cytokine production profile were evaluated after 3 days of incubation. The in-vitro HIV-1 replication was measured in culture supernatants in the seventh day following stimulation. The cytokines were also analyzed in the plasma. RESULTS: Our results demonstrated a lower T-cell proliferation and a lower interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma production in polyclonally activated T-cell cultures from G1 patients, when compared with G2. Furthermore, high levels of interleukin-10 were produced both systemically and by activated T-cell cultures from G1 patients. Interestingly, the neutralization of endogenous interleukin-10 by anti-interleukin-10 monoclonal antibody elevated both the inflammatory cytokines' release and the HIV-1 replication in the polyclonally activated T-cell cultures from G1 patients. Additionally, the maternal antiretroviral treatment significantly enhanced the systemic interleukin-10 production. Finally, the higher systemic interleukin-10 levels were inversely correlated with vertical virus transmission risk. CONCLUSION: These results indicate that a high tendency of pregnant women to produce interleukin-10 can help them control the HIV-1 replication, and this can reduce the risk of vertical transmission. Furthermore, our data suggest a role for maternal antiretroviral treatment in enhancing this phenomenon.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/fisiología , Interleucina-10/biosíntesis , Complicaciones Infecciosas del Embarazo/inmunología , Replicación Viral/inmunología , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Proliferación Celular , Células Cultivadas , Citocinas/biosíntesis , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Subgrupos de Linfocitos T/inmunología , Células TH1/inmunología , Replicación Viral/efectos de los fármacos , Adulto JovenRESUMEN
The cell surface carbohydrates of four strains of Aeromonas caviae were analyzed by agglutination and lectin-binding assays employing twenty highly purified lectins encompassing all sugar specificities. With the exception of L-fucose and sialic acid, the sugar residues were detected in A. caviae strains. A marked difference, however, in the pattern of cell surface carbohydrates in different A. caviae isolates was observed. Specific receptors for Tritricum vulgaris (WGA), Lycopersicon esculentum (LEL) and Solanum tuberosum (STA) (D-GlcNAc-binding lectins) were found only in ATCC 15468 strain, whereas Euonymus europaeus (EEL, D-Gal-binding lectin) sites were present exclusively in AeQ32 strain, those for Helix pomatia (HPA, D-GalNAc-binding lectin) in AeC398 and AeV11 strains, and for Canavalia ensiformes (Con A, D-Man-binding lectin) in ATCC 15468, AeC398, AeQ32 and AeV11 strains, after bacterial growing at 37ºC. On the other hand, specific receptors for WGA and EEL were completely abrogated growing the bacteria at 22ºC. Binding studies with 125I- labeled lectins from WGA, EEL and Con A were performed. These assays essentially confirmed the selectivity, demonstrated in the agglutination assays of these lectins for the A. caviae strains.
Os carboidratos de superfície celular de quatro amostras de Aeromonas caviae foram analisados por aglutinação e ensaios de ligação de lectinas empregando vinte lectinas altamente purificadas com especificidade para açúcares. Com exceção da L-fucose e do ácido siálico, os resíduos de açúcar foram detectados em amostras de A. caviae. Entretanto, foi observada uma diferença marcante no padrão de carboidratos de superfície celular em diferentes amostras de A. caviae. Receptores específicos para Tritricum vulgaris (WGA), Lycopersicon esculentum (LEL) e Solanum tuberosum (STA), lectinas de ligação a D-GlcNAc, foram encontrados apenas na amostra ATCC 15468, enquanto sítios de Euonymus europaes (EEL), lectina de ligação a D-Gal, estavam presentes exclusivamente na amostra AeQ32, sítios de Helix pomatia (HPA), lectina de ligação a D-GalNac, nas amostras AeC398 e AeV11 e de Canavalia ensiformis (Com A), lectina de ligação a D-Man, nas amostras ATCC 15468, AeC398, AeQ32 e AeV11, após crescimento bacteriano a 37ºC. Por outro lado, receptores específicos para WGA e EEL foram completamente abolidos após o crescimento das bactérias a 22ºC. Estudos de ligação com lectinas WGA, EEL e Con A marcadas com 125I também foram realizados. Esses ensaios confirmaram a seletividade, demonstrada em ensaios de aglutinação dessas lectinas para as amostras de A. caviae.
Asunto(s)
Humanos , Niño , Aeromonas/aislamiento & purificación , Carbohidratos/análisis , Técnicas In Vitro , Lectinas/análisis , Aglutinación , Medios de Cultivo , MétodosRESUMEN
This work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from mothers who control (G1) or not (G2) the plasma viral load, using unexposed neonates as controls. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, IFN-gamma and TNF-alpha were significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from anti-retroviral treated mothers. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-retroviral treatment to attenuate it.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/virología , Proliferación Celular , Femenino , Antígenos VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/metabolismo , Humanos , Inmunidad Materno-Adquirida , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Activación de Linfocitos , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Carga ViralRESUMEN
The cell surface carbohydrates of four strains of Aeromonas caviae were analyzed by agglutination and lectin-binding assays employing twenty highly purified lectins encompassing all sugar specificities. With the exception of L-fucose and sialic acid, the sugar residues were detected in A. caviae strains. A marked difference, however, in the pattern of cell surface carbohydrates in different A. caviae isolates was observed. Specific receptors for Tritricum vulgaris (WGA), Lycopersicon esculentum (LEL) and Solanum tuberosum (STA) (D-GlcNAc-binding lectins) were found only in ATCC 15468 strain, whereas Euonymus europaeus (EEL, D-Gal-binding lectin) sites were present exclusively in AeQ32 strain, those for Helix pomatia (HPA, D-GalNAc-binding lectin) in AeC398 and AeV11 strains, and for Canavalia ensiformes (Con A, D-Man-binding lectin) in ATCC 15468, AeC398, AeQ32 and AeV11 strains, after bacterial growing at 37°C. On the other hand, specific receptors for WGA and EEL were completely abrogated growing the bacteria at 22°C. Binding studies with (125)I- labeled lectins from WGA, EEL and Con A were performed. These assays essentially confirmed the selectivity, demonstrated in the agglutination assays of these lectins for the A. caviae strains.
RESUMEN
OBJECTIVE: To evaluate the impact of age on the proliferative response, cytokine profile and viral kinetics in AIDS patients treated successfully with antiretroviral drugs. METHODS: Peripheral blood mononuclear cells (PBMC), CD4 cell-depleted PBMC or CD4 T cells from young adult and aged HIV-1-infected patients were activated in vitro with anti-CD3 with or without interleukin (IL)-2. Lymphoproliferation and cytokines were measured after 3 days and in-vitro HIV-1 replication after 7 days. RESULTS: Both lymphoproliferation and cytokine [IL-1beta, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)] secretion were higher in younger than in older AIDS patients. In cultures of cells derived from aged patients and activated by anti-CD3, IFN-gamma production was severely damage and IL-10 production was much higher. Although IL-2 addition to activated PBMC elevated IFN-gamma secretion, IL-10 production remained elevated in the aged group. The depletion of CD4 T lymphocytes from these cultures dramatically reduced released IL-10 in the older group but did not alter significantly IFN-gamma production. Interestingly, higher IL-10 levels produced by CD4 T cells were related to lower in-vitro HIV-1 replication, and the blockade of this cytokine by anti-IL-10 monoclonal antibody enhanced virus replication. This effect may be correlated with elevated TNF-alpha secretion. Finally, impaired IFN-gamma secretion detected in activated CD4 T cells obtained from aged patients was not directly correlated with high IL-10 production. CONCLUSIONS: Elevated IL-10 production by aged AIDS patients contributed considerably to control of HIV replication and to inhibition of TNF-alpha secretion but not to the reduced IFN-gamma production.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Linfocitos T CD4-Positivos/inmunología , VIH-1/fisiología , Interleucina-10/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Anciano , Envejecimiento/inmunología , Terapia Antirretroviral Altamente Activa , Proliferación Celular , Células Cultivadas , Citocinas/biosíntesis , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Interferón gamma/biosíntesis , Activación de Linfocitos/inmunología , Persona de Mediana Edad , Replicación ViralRESUMEN
Um paciente do sexo masculino, 26 anos, branco, casado, com o nível de escolaridade fundamental, residente no município de Duque de Caxias, Rio de Janeiro, foi atendido no Ambulatório do Instituto de Dermatologia Rubem David Azulay na Santa Casa de Misericórdia do Rio de Janeiro, em março de 2005, com queixa inicial de verruga peniana clássica, sugestiva, pela avaliação clínica, de um caso de HPV. Foi solicitada então como exame complementar a testagem sorológica para sífilis, aconselhada a realização do exame para detecção de anticorpos para o vírus HIV e foi sugerido também que ele trouxesse a sua parceira sexual para avaliação clínica. A realização do teste não treponêmico de sífilis, o VDRL (Veneral Disease Research Laboratory), foi reator 1:16, sendo confirmado pelo teste treponêmico TPHA (Treponema pallidum Hemaglutination Assay). O paciente não voltou para a consulta agendada, só retornando, cinco meses depois, acompanhado da esposa grávida de cinco meses. Ambos foram tratados de acordo com os protocolos do Ministério da Saúde. Na análise desse caso foram evidenciadas várias facetas das co-infecções das doenças sexualmente transmissíveis (DST).
A patient, male, 26 years old, married, with elementary school ship, lived in Duque de Caxias, Rio de Janeiro, Brazil, came for the clinical of Sexually Transmited Disease (STD) in Rubem David Azulay Dermatology Institute in Santa Casa de Misericórdia, Rio de Janeiro, with the principal complaint of a wart in his penis. After the first clinical evaluation, it was concluded that it was a case of human papilomavirus, the HPV. He was solicited complementary exams to detect syphilis and he was advised to make a test to detect antibody for HIV, he was also suggested that it was important to bring his wife in the next consult for evaluation. When the syphilis test of VDRL (Veneral Disease Research Laboratory) was realized it was detected a title of 1:16, it was confirmed with T.P.H.A.( Treponema pallidum Hemaglutination Assay), a treponema test. Unfortunately the patient didnt come in the following consult, only regressing five months later. In this occasion he brought his wife, she was five months of pregnancy. Both of them was treated in accord of the protocol of the Health Ministry. In this Case of Study it was evidenced the relationship of co-infection in the sexually transmitted disease (STD).