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BACKGROUND: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1ß, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. METHODS: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/BS9GM . A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. RESULTS: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). CONCLUSION: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis.

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Pig is one of the most consumed meats worldwide. One of the main conditions for pig production is Porcine Enteropathy caused by Lawsonia intracellularis. Among the effects of this disease is chronic mild diarrhea, which affects the weight gain of pigs, generating economic losses. Vaccines available to prevent this condition do not have the desired effect, but this limitation can be overcome using adjuvants. Pro-inflammatory cytokines, such as interleukin 18 (IL-18), can improve an immune response, reducing the immune window of protection. In this study, recombinant porcine IL-18 was produced and expressed in Escherichia coli and Pichia pastoris. The protein's biological activity was assessed in vitro and in vivo, and we determined that the P. pastoris protein had better immunostimulatory activity. A vaccine candidate against L. intracellularis, formulated with and without IL-18, was used to determine the pigs' cellular and humoral immune responses. Animals injected with the candidate vaccine co-formulated with IL-18 showed a significant increase of Th1 immune response markers and an earlier increase of antibodies than those vaccinated without the cytokine. This suggests that IL-18 acts as an immunostimulant and vaccine adjuvant to boost the immune response against the antigens, reducing the therapeutic window of recombinant protein-based vaccines.

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Abstract Introduction: This study investigated the correlation between the levels of long noncoding ribonucleic acids (lncRNAs) AF131217.1 and coronary slow flow (CSF). Methods: A total of 22 patients in the high-sensitivity C-reactive protein (hsCRP) group diagnosed with CSF from January 2018 to December 2018 were enrolled in this study. Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) method. Results: LncRNA AF131217.1 expression in the CSF model was activated. Mean TFC was positively correlated with lncRNA AF131217.1 levels and hsCRP levels. LncRNA AF131217.1 induced inflammation factor levels in the in vitro model. Micro ribonucleic acid (miR)-128-3p is a target spot of lncRNA AF131217.1 on the inflammation in vitro model via Kruppel-like factor (KLF) 4. MiR-128-3p reduced inflammation factor levels (tumor necrosis factor alpha, interleukin [IL]-6, IL-1β, and IL-18). Conclusion: Thus, lncRNA AF131217.1 promoted inflammation in the regulated CSF via KLF4 by miR-128-3p.

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Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

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Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1ß and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

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ABSTRACT Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Subjects and methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

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OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

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INTRODUCTION: This study investigated the correlation between the levels of long noncoding ribonucleic acids (lncRNAs) AF131217.1 and coronary slow flow (CSF). METHODS: A total of 22 patients in the high-sensitivity C-reactive protein (hsCRP) group diagnosed with CSF from January 2018 to December 2018 were enrolled in this study. Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) method. Results: LncRNA AF131217.1 expression in the CSF model was activated. Mean TFC was positively correlated with lncRNA AF131217.1 levels and hsCRP levels. LncRNA AF131217.1 induced inflammation factor levels in the in vitro model. Micro ribonucleic acid (miR)-128-3p is a target spot of lncRNA AF131217.1 on the inflammation in vitro model via Kruppel-like factor (KLF) 4. MiR-128-3p reduced inflammation factor levels (tumor necrosis factor alpha, interleukin [IL]-6, IL-1ß, and IL-18). Conclusion: Thus, lncRNA AF131217.1 promoted inflammation in the regulated CSF via KLF4 by miR-128-3p.

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Psoriasis is a chronic immunoinflammatory skin disease. Although its diagnosis is clinical, differences in the appearance and severity of lesions pose a challenge for clinicians worldwide. The use of accessible biomarkers for psoriasis could aid in the early diagnosis and treatment of the disease. To date, evidence on the analysis of gingival crevicular fluid (GCF) molecules as novel, accessible, and reliable biomarkers for psoriasis is limited. This cross-sectional study compared the GCF levels of IL-18, soluble (s)ICAM-1, and sE-selectin in psoriatic patients (n = 42) and healthy controls (n = 39). Individuals with psoriasis not undergoing treatment and healthy individuals were included independent of periodontal status. GCF samples were collected, and a multiplex bead immunoassay was performed to quantify the levels of the target molecules. Psoriatic patients presented higher concentrations of IL-18 and lower concentrations of sE-selectin compared to controls (p < 0.05). No differences were found in the levels of sICAM-1 between the two groups (p > 0.05). Psoriasis was associated with IL-18 and E-selectin levels regardless of periodontal status, age, and smoking habit (p < 0.05). The areas under the receiver operating characteristic curve (ROC) for IL-18 and sE-selectin were 0.77 and 0.68, respectively. In conclusion, IL-18 and sE-selectin levels in the GCF could be promising biomarker for psoriasis.

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Abstract Background: Migraines are headaches caused by changes in the trigeminovascular metabolic pathway. Migraine headache attacks are associated with neurovascular inflammation, but their pathophysiological mechanisms have not been fully explained. Objective: To investigate the relationship between serum vaspin, visfatin, chemerin and interleukin-18 (IL-18) levels and the frequency of attacks in migraine headache. Methods: Three groups were established: migraine with aura (n = 50), migraine without aura (n = 50) and control group (n = 50). The migraine diagnosis was made in accordance with the International Classification of Headache Disorders-III beta diagnostic criteria. The analyses on serum vaspin, visfatin, chemerin and IL-18 levels were performed using the enzyme-linked immunosorbent assay method. Results: The serum vaspin, visfatin, chemerin and IL-18 levels were found to be significantly higher in the migraine patients than in the control group (p < 0.01). No statistically significant differences in serum vaspin, visfatin, chemerin and IL-18 levels were found among the migraine patients during attacks or in the interictal period (p>0.05). The serum visfatin and chemerin levels of the migraine patients were positively correlated with their serum IL-18 levels (p < 0.01), while their serum chemerin and visfatin levels were positively correlated with their serum vaspin levels (p < 0.05). Conclusions: This study showed that these biomarkers may be related to migraine pathogenesis. Nonetheless, we believe that more comprehensive studies are needed in order to further understand the role of vaspin, visfatin, chemerin and IL-18 levels in the pathophysiology of migraine headaches.

Resumo Introdução: A migrânea é causada por alterações nas vias metabólicas do sistema trigeminovascular. Crises de migrânea estão associadas à inflamação neurovascular, mas seus mecanismos patofisiológicos ainda não são totalmente explicados. Objetivo: Investigar a relação entre níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) e a frequência de crises de migrânea. Métodos: Três grupos foram formados: migrânea com aura (n = 50), migrânea sem aura (n = 50) e grupo controle (n = 50). A migrânea foi diagnosticada de acordo com os critérios da Classificação Internacional das Cefaleias (ICHD-III). As análises dos níveis séricos de vaspina, visfatina, quemerina e IL-18 foram realizadas utilizando-se o método imunoenzimático (ELISA). Resultados: Os níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) foram significativamente mais elevados em pacientes com migrânea do que no grupo controle (p < 0.01). Nenhuma diferença estatisticamente significativa foi observada nos níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) entre os pacientes com migrânea durante crises ou no período interictal (p>0,05). Os níveis séricos de visfatina e quemerina em pacientes com migrânea se correlacionaram positivamente com os níveis séricos de IL-18 (p < 0,01), ao passo que os níveis séricos de quemerina e visfatina se correlacionaram positivamente com os níveis séricos de vaspina (p < 0,05). Conclusões: Este estudo demonstrou que estes biomarcadores podem estar relacionados à patogênese da migrânea. Contudo, acreditamos que estudos mais abrangentes são necessários a fim de melhor compreendermos o papel dos níveis de vaspina, visfatina, quemerina e IL-18 na fisiopatologia da migrânea.

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O líquen plano oral (LPO) é uma condição imuno-inflamatória mucocutânea crônica que ainda possui etiologia e patogênese desconhecidas. Estudos mostrando a participação de citocinas no LPO, em especial, interleucinas (IL)-6, IL-17 e IL-18, são escassos, assim como a correlação das características clínicas e histológicas das lesões de LPO com a presença destes mediadores inflamatórios. Todas as lesões de LPO e de lesões liquenoides orais (LLO) foram revisadas a partir do arquivo do laboratório de Patologia Bucal da Faculdade de Odontologia da Universidade do Estado do Rio de Janeiro e as características clínico-patológicas dos casos foram analisadas. Foram selecionados 40 casos de LPO para realização adicional de reações imuno-histoquímicas para IL-6, IL-17 e IL-18. A amostra total foi composta por 221 casos e mostrou que o LPO apresentou predileção por mulheres adultas, mais frequentemente acometidas pelo padrão reticular e com lesões localizadas predominantemente na mucosa jugal. Os 40 casos selecionados para a avaliação imuno-histoquímica incluíram pacientes com média de idade de 53 anos, sem predileção por gênero, e com lesões localizadas preferencialmente na mucosa jugal (85%), na gengiva/mucosa alveolar (47%) e na língua (42%). Quanto ao padrão clínico, 14 pacientes (35%) mostravam lesões exclusivamente reticulares e 26 (65%) mostravam lesões reticulares associadas a lesões atrófico-erosivas. Sintomas foram relatados por 53% dos pacientes e incluíram principalmente ardência e desconforto local. A análise histológica mostrou que o epitélio das lesões mostrava espessura normal, atrófica ou hiperplásica em, respectivamente, 17 (43%), 9 (22%) e 14 (35%) casos. A presença de hiperqueratose foi observada em 21 casos (53%) e exocitose de linfócitos T CD4+ e T CD8+ estava presente em, respectivamente, 17 (42%) e 30 (75%) casos. A análise imuno-histoquímica revelou que a IL-6 foi, de forma geral, a mais expressa, tanto no epitélio, quanto no conjuntivo. A expressão de IL-17 se mostrou intensa no tecido conjuntivo, em 40% dos casos. A IL-18 mostrou intensidade mais frequente leve/moderada tanto no epitélio (40%), quanto no tecido conjuntivo (45%). A presença de exocitose mostrou relação com a maior expressão das ILs e a expressão de IL-17 foi maior no epitélio mostrando hiperqueratose. Os resultados do presente estudo mostraram que as características clínicas das lesões de LPO e de LLO são distintas e podem ser utilizadas para diferenciação entre as duas entidades. Os achados histológicos e imunohistoquímicos sugerem que as ILs estudadas mostram-se mais presentes quando há exocitose linfócitos T CD4+ e T CD8+ e que sua expressão pode ter relação com as alterações epiteliais encontradas no LPO, participando da patogênese e da modulação da expressão da doença.

Oral lichen planus (OLP) is a chronic immunoinflammatory mucocutaneous condition of unknown etiology and pathogenesis. Studies focusing on the presence of cytokines in OLP, especially interleukin (IL)-6, IL-17 and IL-18, are scarce, as well as the correlation of clinical and histological characteristics with the presence of inflammatory mediators. All lesions diagnosed as OLP and oral lichenoid lesions (OLL) were reviewed from the files of the Oral Pathology laboratory, Dental School, Rio de Janeiro State University, and their clinicopathological characteristics were analyzed. Forty cases diagnosed as OLP were selected for additional immunohistochemical reactions directed against IL-6, IL-17 e IL-18. The total sample was composed by 221 cases and showed that OLP presented a predilection for adult females, mostly affected by lesions with the reticular pattern and located in the buccal mucosa. The 40 cases selected for the immunohistochemical reactions included patients with a mean age of 53 years, with no gender predilection, and with lesions located mostly in the buccal mucosa (85%), gingiva/alveolar mucosa (47%) and tongue (42%). The clinical pattern showed reticular lesions in 14 patients (35%) and reticular and atrophic/erosive lesions in 26 patients (65%). Symptoms were reported by 53% of the patients and included mostly burning sensation and local discomfort. Histological analysis showed that the epithelial thickness was normal, atrophic, or hyperplastic in, respectively, 17 (43%), 9 (22%) and 14 (35%) cases. The presence of hyperkeratosis was observed in 21 cases (53%), and exocytosis of T CD4+ and T CD8+ lymphocytes was present in, respectively, 17 (42%) and 30 (75%) cases. Immunohistochemical analysis showed that, in general, IL-6 was the most expressed IL both in epithelium and connective tissue. IL-17 expression was considered intense in the connective tissue from 40% of the cases. IL-18 expression was considered mostly mild/moderate both in epithelium (40% of the cases) and connective tissue (45% of the cases). The presence of exocytosis was associated with a higher expression of the ILs and expression of IL-17 was higher in epithelium showing hyperkeratosis. The results from the present study showed that the clinical characteristics of OLP and OLL are distinct and can be useful in differentiating these two diagnostic entities. The histological and immunohistochemical features suggest that the studied ILs are more expressed when there is exocytosis of both T CD4+ and T CD8+ lymphocytes. Expression of the ILs can be associated with the epithelial alterations encountered in OLP, participating in the pathogenesis and modulating the expression of the disease.

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Resumo Fundamento Pacientes com infarto agudo do miocárdio podem apresentar uma grande área infartada e disfunção ventricular mesmo com trombólise e revascularização precoces. Objetivo Investigar o comportamento das citocinas circulantes em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) e a relação delas com a função ventricular. Métodos No estudo BATTLE-AMI (Avaliação dos Linfócitos Tipos B e T no Infarto Agudo do Miocárdio), os pacientes com IAMCSST foram tratados com uma estratégia farmacoinvasiva. Os níveis de citocinas (IL-1β, IL-4, IL-6, IL-10 e IL-18) no plasma foram testados através de ensaio de imunoadsorção enzimática (ELISA) no início do estudo e após 30 dias. A massa infartada e a fração de ejeção ventricular esquerda (FEVE) foram examinadas por ressonância magnética cardíaca 3-T. Valores de p menores que 0,05 foram considerados significativos. Resultados Na comparação com o início do estudo, níveis mais baixos foram detectados para IL-1β (p = 0,028) e IL-18 (p < 0,0001) após 30 dias do IAMCSST, enquanto níveis mais altos foram observados para IL-4 (p = 0,001) e IL-10 (p < 0,0001) no mesmo momento. Em contrapartida, nenhuma mudança foi detectada nos níveis de IL-6 (p = 0,63). Os níveis da proteína C-reativa de alta sensibilidade e de IL-6 se correlacionaram no início do estudo (rho = 0,45, p < 0,0001) e 30 dias após o IAMCSST (rho = 0,29, p = 0,009). No início do estudo, a correlação entre os níveis de IL-6 e FEVE também foi observada (rho = -0,50, p = 0,004). Conclusões Durante o primeiro mês pós-infarto agudo do miocárdio, observamos uma melhora significativa no balanço das citocinas pró e anti-inflamatórias, exceto da IL-6. Esses achados sugerem risco inflamatório residual. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Patients with acute myocardial infarction may have a large infarcted area and ventricular dysfunction despite early thrombolysis and revascularization. Objective To investigate the behavior of circulating cytokines in patients with ST-segment elevation myocardial infarction (STEMI) and their relationship with ventricular function. Methods In the BATTLE-AMI (B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction) trial, patients with STEMI were treated with a pharmacoinvasive strategy. The plasma levels of cytokines (IL-1 β , IL-4, IL-6, IL-10, and IL-18) were tested using enzyme-linked immunosorbent assay (ELISA) at baseline and after 30 days. Infarcted mass and left ventricular ejection fraction (LVEF) were examined by 3-T cardiac magnetic resonance imaging. All p-values < 0.05 were considered statistically significant. Results Compared to baseline, lower levels were detected for IL-1 β (p = 0.028) and IL-18 (p < 0.0001) 30 days after STEMI, whereas higher levels were observed for IL-4 (p = 0.001) and IL-10 (p < 0.0001) at that time point. Conversely, no changes were detected for IL-6 levels (p = 0.63). The levels of high-sensitivity C-reactive protein and IL-6 correlated at baseline (rho = 0.45, p < 0.0001) and 30 days after STEMI (rho = 0.29, p = 0.009). At baseline, correlation between IL-6 levels and LVEF was also observed (rho = -0.50, p = 0.004). Conclusions During the first month post-MI, we observed a marked improvement in the balance of pro- and anti-inflammatory cytokines, except for IL-6. These findings suggest residual inflammatory risk. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

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Abstract Objective: To provide a new interpretation of the effect of intraoperative hemodynamic data on postoperative acute kidney injury (AKI) development and to determine the accuracy of some biomarkers which are thought to be the early markers of renal injury. Methods: One hundred adult patients who were connected to the heart-lung pump during open-heart surgery were included in this study. Hemodynamic data, oxygen delivery, and transfusions were recorded intraoperatively, and the preoperative and 3. postoperative hour cystatin C, interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) parameters were measured for early detection of kidney damage. In the analysis, 95% significance level was used to determine the difference. Results: According to the Kidney Disease Improving Global Outcomes criterion, AKI developed in 24 patients, 18 of whom were stage 1, two were stage 2, and four were stage 3. AKI (+) patients had more transfusions in the intraoperative period and AKI development was a risk factor for postoperative complications. NGAL and IL-18 levels were found to be approximately two-fold in the postoperative period in AKI (+) patients, whereas cystatin C was not sensitive in AKI detection. Conclusion: AKI development increases the risk of postoperative complications. NGAL and IL-18 were successful in detecting AKI in the early postoperative period.

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Resumo Fundamento A insuficiência coronariana constitui a principal causa de morte no mundo, e a identificação de pacientes de maior risco para doença arterial coronariana (DAC) constitui um desafio. Objetivos Testar os biomarcadores interleucina 18 (IL-18) e proteína precursora do trombo (TpP), envolvidos na aterogênese, para auxílio na avaliação precoce de DAC. Métodos Coorte transversal de 119 pacientes, estratificados em três grupos: Grupo I - síndrome coronariana aguda (39); Grupo II - DAC crônica (40); e Grupo III - controle, sem lesão coronariana, mas podendo apresentar fatores de risco para DAC (40). Análise estatística através do programa estatístico SPSS (Statistical Package for the Social Sciences) para Windows versão 17.0 de 2008. Fixou-se em 0,05 ou 5% (p<0,05) nível de significância e intervalo de confiança de 95%. Teste do qui-quadrado (χ2). Análise de variância (ANOVA), Teste de Tukey. Resultados Idade média, 60,36±9,64 anos; prevalência do sexo feminino no Grupo III (65,0% p=0,002), porém sem significado estatístico para os valores médios de IL-18 e TpP. Os valores médios de IL-18 e TpP mostravam-se aumentados no Grupo I, quando comparados aos valores dos demais grupos: IL-18 = 1325,44±1860,13 ng/dL, p=0,002; TpP = 35,86±28,36 µg/mL, p<0,001. Na comparação dois a dois, observou-se que o Grupo I apresentou valor médio de IL-18 e TpP maior que o do Grupo II (IL-18 = 353,81±273,65 ng/dL; TpP = 25,66±12,17 µg/mL) e o do Grupo III (IL-18 = 633,25±993,93 ng/dL; TpP=18,00±8,45 µg/mL). Conclusão Na vigência de DAC aguda, houve elevação desses biomarcadores, sugerindo relação com o processo de instabilidade da placa aterosclerótica, mas não com a fase crônica. (Arq Bras Cardiol. 2020; 114(4):692-698)

Abstract Background Coronary failure is the leading cause of death worldwide and identifying patients at higher risk for coronary artery disease (CAD) is a challenge. Objectives To test the biomarkers interleukin 18 (IL-18) and thrombus precursor protein (TpP), involved in atherogenesis, to aid in the early assessment of CAD. Methods This was a cross-sectional cohort of 119 patients, stratified into three groups: Group I - acute coronary syndrome (39); Group II - chronic CAD (40) and Group III - control, without coronary lesion, but who might have risk factors for CAD (40). Statistical analysis was performed using the statistical program SPSS (Statistical Package for the Social Sciences) for Windows ,version 17.0 of 2008. The significance level was set at 0.05 or 5% (p <0.05), with a 95% confidence interval. Chi-square test (χ2), Analysis of variance (ANOVA), and Tukey's test were used. Results The mean age was 60.36 ± 9.64 years; there was a prevalence of females in Group III (65.0% p = 0.002), but without statistical significance for the means of IL-18 and TpP. The means of IL-18 and TpP were increased in Group I when compared to the other groups; IL-18 = 1325.44 ± 1860.13 ng/dL, p = 0.002; TpP = 35.86 ± 28.36 µg / mL, p <0.001). When compared two-by-two, it was observed that Group I had higher mean IL-18 and TpP values than Group II (IL-18 = 353.81 ± 273.65 ng / dL; TpP = 25.66 ± 12, 17 µg / mL) and Group III (IL-18 = 633.25 ± 993.93 ng / dL; TpP = 18.00 ± 8.45 µg / mL). Conclusion There was an increase in these biomarkers in acute CAD, suggesting a relationship with the atherosclerotic plaque instability process, but not with the chronic phase. (Arq Bras Cardiol. 2020; 114(4):692-698)

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BACKGROUND: Interleukin-18 (IL-18), a proinflammatory and proatherogenic cytokine, has been associated with type 2 diabetes, metabolic syndrome, stroke and coronary artery disease. Some studies have indicated that the IL-18 promoter -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of cardiovascular disease (CVD). The aim of this study was to evaluate the association between -137 G/C polymorphism and the levels of IL-18, biochemical markers for cardiovascular disorders, anthropometric profile and cardiovascular disease in Brazilian patients with type 2 diabetes (T2DM). DESIGN & METHODS: Study subjects comprised 125 T2DM patients undergoing follow-up at a reference endocrinology service in northeastern Brazil. The -137G/C polymorphism in the IL-18 gene and serum IL-18 levels were determined by using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay (ELISA), respectively. The anthropometric parameters were assessed using a Body Composition Monitor with Scale, and the laboratory data were measured using an automatic analyzer as well as spectrophotometric analysis. RESULTS: The genotype distribution of IL-18 -137 G/C genetic polymorphism was significantly different among T2DM patients with and without CVD. The results show an association between the CC genotype of -137G/C polymorphism and CVD in T2DM patients (p < 0.001). Serum levels of IL-18 were significantly higher in CC carriers (843.1 pg/mL) compared with GG or GC carriers (303.6 pg/mL and 292.0 pg/mL, respectively). In addition, the present study showed that carriers of the CC genotype also had significantly higher concentrations of creatinine and albuminuria than carriers of the GG or GC genotypes (p < 0.05 in both). CONCLUSION: These results suggest that Brazilian T2DM patients with the CC genotype seem to show a predisposition to CVD, as well as an elevation in markers of renal function.

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OBJECTIVE: Synovial fluid (SF) plays an important role in the maintenance of articular cartilage. SF is a dynamic reservoir of proteins derived from cartilage and synovial tissue; thus, its composition may serve as a biomarker that reflects the health and pathophysiological condition of the joint. The purpose of the current study was to evaluate the osteoarthritic synovial fluid (OASF) and transforming growth factor-ß1 (TGF-ß1) activity in articular chondrocytes catabolic and inflammatory responses. DESIGN: Chondrocytes were seeded at passage 2 and cultured for 72 hours under different conditions. Human chondrocytes were subjected to OASF while rat chondrocytes were subjected to either healthy synovial fluid (rSF) or TGF-ß1 and then assigned for cell viability analysis. In addition, the effects of OASF and TGF-ß1 on chondrocytes metalloprotease (MMP)-3 and MMP-13 and interleukin-18 (IL-18) expression were evaluated by immunocytochemistry, ELISA, and reverse transcriptase-polymerase chain reaction. RESULTS: SF from osteoarthritic patients significantly induced MMP-3, MMP-13, and IL-18 receptor expression in chondrocytes. To put in evidence the inflammatory activity of OASF, healthy chondrocytes from rat were cultured with TGF-ß1. In the presence of TGF-ß1 these cells started to express MMP-3, MMP-13, and IL-18 genes and attached to each other forming a chondrocyte aggregated structure. Healthy SF was able to maintain a typical monolayer of rounded chondrocytes with no inflammatory response. CONCLUSION: In summary, these observations demonstrated that TGF-ß1, one of the components of OASF, has a dual effect, acting in chondrocyte maintenance and also inducing inflammatory and catabolic properties of these cells.

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AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days. RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred. CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo.

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3.1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001). A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in vivo.

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AIM: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. The signs of inflammation such as hyperemia and hyperthermia might suggest the possible participation of inflammatory mediators. This study investigates stromal and tumor expression of nuclear factor-kappa B (NF-κB) and interleukin-18 (IL-18) in samples obtained from IBC and noninflammatory locally advanced breast cancer (LABC) and the influence of these markers on patients' prognosis. METHODS: Demographic data, tumor molecular characteristics and overall survival in both groups were also assessed. Furthermore, in this study, we evaluated the expression of IL-18 and p50 nuclear fraction of NF-κB by immunohistochemistry in specimens from IBC and LABC (T4b). RESULTS: We observed that 24.6% of women were diagnosed with IBC up to age 40. In addition, the patients with IBC showed a lower overall survival when compared to LABC. In regard to molecular markers, ER+ , C-erbB2- or triple negative IBC patients showed a significantly reduced overall survival. In addition, a higher IL-18 immunostaining in stroma of IBC and LABC was observed in comparison with tumor cells, but stromal immunoexpression was similar between IBC and LABC. Besides, IL-18 positivity seemed be related with a better clinical response to neoadjuvant chemotherapy. However, NF-κB expression was identical in both groups. CONCLUSION: The IL-18 is present in tumor stroma of IBC and LABC and seems to be associated with the complete response to neoadjuvant chemotherapy.

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