Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome.

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1ß (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1ß and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.

Cytokine profiles and their correlation with clinical and blood parameters in rheumatoid arthritis and systemic lupus erythematosus.

The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal-Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1ß, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

Immunologic mediators profile in COVID-19 convalescence.

SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal-Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

Synergistic Antifungal Effect and In Vivo Toxicity of a Monoterpene Isoespintanol Obtained from Oxandra xylopioides Diels.

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.

Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota-Gut-Brain Axis: A Pilot Clinical Study.

Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut-brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin's impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.

Blunted inflammatory response is associated with a lower response to a weight loss dietary intervention in liver recipients.

BACKGROUND & AIMS: Obesity is associated with chronic low-grade inflammation, and adipose tissue inflammation is required for fatty tissue remodeling. Interestingly, immunosuppressed patients, as liver transplant recipients, often experience excessive weight gain. We investigated how liver recipients' inflammatory response affects body weight loss induced by dietary treatment. METHODS: Overweight liver recipients were paired with non-transplanted subjects to compare their peripheral immune profiles. RESULTS: Transplanted patients had similar profiles of peripheral blood mononuclear cells compared to controls but lower CD8lowCD56+CD16+NK cells and higher B lymphocytes. Patients showed lower serum concentrations of IFN-γ, TNF, IL-4, IL-2, and IL-10 and lower inflammatory responsiveness of peripheral blood mononuclear cells under inflammatory stimuli. Liver recipients paired with non-transplanted subjects followed a weight loss dietary plan for 6 months to verify body composition changes. After 3 and 6 months of nutritional follow-up, the control group lost more body weight than the liver recipient group. The control group decreased fat mass and waist circumference, which was not observed in transplanted patients. CONCLUSION: Therefore, liver recipients under immunosuppressant treatment responded less to different inflammatory stimuli. This impaired inflammatory milieu might be implicated in the lack of response to weight loss dietary intervention. Inflammation may be essential to trigger the weight loss induced by dietary prescription. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identification number: NCT03103984.

Landscape of in situ cytokine expression, soluble C-type lectin receptors, and vitamin D in patients with recurrent vulvovaginal candidiasis.

The immunopathogenesis of recurrent vulvovaginal candidiasis (RVVC) is poorly understood. Recently, it was reported that patients with RVVC present a decrease in both the fungicidal capacity of neutrophils and the proliferative capability of peripheral blood mononuclear cells in response to Candida albicans infection, suggesting an alteration in the innate and adaptive immune response. The aim of this study was to determine the in-situ expression, in the vaginal mucosa, of genes associated with the immune response, as well as the serum concentrations of dectin-1, mannose-binding lectin (MBL), and vitamin D in patients with RVVC. A study was carried out on 40 patients with a diagnosis of RVVC and 26 healthy women. Vaginal scrapings were obtained, and the expression of genes that encode cytokines and transcription factors specific for Th1, Th2, Th17, Treg, pro-inflammatory profiles, and enzymes related to oxidative/microbicidal mechanisms was evaluated by quantitiative polymerase chain reaction (qPCR). Additionally, serum levels of vitamin D and the soluble receptors dectin-1 and MBL were determined by enzyme-linked immunosorbent assay (ELISA). In patients with RVVC, a decreased expression of T-bet, RORγ-T, IL-1ß, and IL-17, and an increase in the expression of FOXP3, IL-4, IL-8, IL-10, and IL-18 were observed when compared to healthy women: moreover, decreased levels of MBL were also observed in these patients. These results confirm that patients with RVVC present in-situ alterations in both the specific and adaptive immune response against Candida spp., a fact that could be associated with the exaggerated vaginal inflammatory response.

The study concerns the immune response of women with recurrent vulvovaginal candidiasis; we observed an alteration in the expression of genes that participate in the control of infection, a fact that could be associated with the exaggerated vaginal inflammatory response observed in those patients.

Assessment of immune responses to a Comirnaty® booster following CoronaVac® vaccination in healthcare workers.

BACKGROUND: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.

Plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacterial pulmonary disease.

We investigated the value of plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacteria (NTM) pulmonary disease. Plasma cytokine levels were measured and compared among patients with NTM pulmonary disease (n=111), tuberculosis (TB) patients (n=50), and healthy individuals (n=40). Changes during treatment were monitored at 3 and 6 months after treatment. According to the treatment response, NTM patients were classified as 'resistance' or 'sensitivity' responders. The results revealed that five out of twelve cytokines exhibited significantly higher levels in NTM patients compared to controls. Among these, interleukin (IL)-6 demonstrated the strongest discriminating capacity for NTM. Furthermore, when combined with IL-1ß, they efficiently distinguished between NTM drug-resistant and drug-sensitive patients, as well as between NTM and TB groups. Additionally, IL-6 levels initially rose and then decreased in the NTM drug-resistant group during the six months of treatment, similar to the behavior of IL-1ß in the NTM drug-sensitive group. Subgroup analyses of the sensitive group with differential treatment responses revealed an increase in IL-10 levels in the six-month treatment responders. A high IL-6/IL-10 ratio was associated with increased disease severity of NTM and TB. Collectively, combinations of various plasma cytokines, specifically IL-1ß, IL-6, and IL-10, effectively distinguished NTM patients with varying mycobacterial burdens, with IL-6 and IL-10 emerging as potential biomarkers for early treatment response. The combination of IL-6 and IL-1ß demonstrated the highest discriminatory value for distinguishing between NTM-resistant and NTM-sensitive groups as well as between NTM and TB groups.

Predictive biomarkers of mortality in patients with severe COVID-19 hospitalized in intensive care unit.

Objectives: This study was performed to identify predictive markers of worse outcomes in patients with severe COVID-19 in an intensive care unit. Methods: Sixty patients with severe COVID-19, hospitalized in the Intensive Care Unit (ICU) between March and July 2021, were stratified into two groups according to the outcome survivors and non-survivors. After admission to the ICU, blood samples were collected directly for biomarker analysis. Routine hematological and biochemical biomarkers, as well as serum levels of cytokines, chemokines, and immunoglobulins, were investigated. Results: Lymphopenia, neutrophilia, and thrombocytopenia were more pronounced in non-surviving patients, while the levels of CRP, AST, creatinine, ferritin, AST, troponin I, urea, magnesium, and potassium were higher in the non-surviving group than the survival group. In addition, serum levels of IL-10, CCL2, CXCL9, and CXCL10 were significantly increased in patients who did not survive. These changes in the biomarkers evaluated were associated with increased mortality in patients with severe COVID-19. Conclusion: The present study confirmed and expanded the validity of laboratory biomarkers as indicators of mortality in severe COVID-19.

The influence of lactation on insulin and glucose metabolism, lipid profile, and cytokines in pregnant mares.

Glucose metabolism adapts to gestation, resulting in progressive physiological insulin resistance and increased insulin secretion to maintain maternal euglycemia and glucose availability for the developing fetus. These changes can impact mare fertility and maternal and neonatal health. This is the first comparison of body condition, regional adiposity, insulin and glucose dynamics, lipid metabolism, and cytokine production between lactating and non-lactating mares before, during pregnancy, and early postpartum. Twelve pregnancies from 9 broodmares, five nonlactating (NL) and seven lactating (L), were used. Evaluations were performed on the day of ovulation, at 55, 110, 165, 220, 275, and 330 days of gestation (D55, D110, D165, D220, D275, D330) and 21 days postpartum (21pp). Mares in the L group had lower basal insulin and glucose at the beginning of pregnancy, smaller area under the curve of insulin and glucose, and greater insulin sensitivity and glucose tolerance. Resistin was higher in D110 and D165 than in D0, D275, 330 and 21pp, while leptin was higher in D55, and in D110, at D110 it was equal to D0, D220, and D275, but higher than at D330 and D21pp. As for the groups, L presented lower body condition score (BCS), crest neck score (CNS), rump fat thickness (RUM), basal insulin, glucose area under the curve (AUCg), MIRG and higher RISQI, adiponectin and tumor necrosis factor (TNFα). There was no effect over time in non-esterified fatty acids (NEFA) concentrations between the L mares; in the NL, D275 presented higher concentrations than those of D0, D55, and D110, which in turn were equal to the other time points; there were higher concentrations in NL mares than L in samples D165 and D275. In conclusion, a different metabolic profile during pregnancy was detected, and NL mares were closer to the metabolic threshold for the occurrence of metabolic syndrome during pregnancy. Understanding the impacts of these differences on mare's health and their offspring's future is fundamental as most of our recipient mares for embryo transfer are non-lactating. Therefore, we suggest that further studies be performed to evaluate lactation's influence on mares' metabolic parameters.

Senescent CD4+ T-Cell Phenotypes and Inflammatory Milieu in the Coronary and Systemic Circulation in ST-Elevation Myocardial Infarction: An Exploratory Study.

INTRODUCTION: In ST-elevation myocardial infarction (STEMI), inflammation is pivotal, with early senescent CD4+CD28null cells implicated in its pathogenesis. However, the functional phenotype of these cells within the coronary circulation remains unclear. METHODS: We examined CD4+ cell subpopulations in blood samples from the coronary sinus and vena cava of 24 STEMI patients and the cephalic vein of seven healthy controls. RESULTS: Our findings revealed reduced CD4+ cell counts in STEMI patients compared to controls (1,998, 1,275-3,268 vs. 4,278, 3,595-4,449), alongside an increased proportion of CD4+ cells lacking CD28 expression (20.1 vs. 6.1%). These CD4+CD28null cells in STEMI predominantly exhibited a Th1 phenotype (47.8% vs. 6.6%). Intriguingly, no significant differences were detected in CD4+CD28null cells between coronary sinus and vena cava, and cytokine levels in these compartments remained similar. CONCLUSION: CD4+CD28null cells are increased in STEMI, mainly polarized toward a Th1 phenotype, and distributed equally between the different vascular beds.

Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice.

OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice. METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated. RESULTS: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates. CONCLUSION: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

Rehabilitation Intervention Is Associated With Improved Neurodevelopment and Modulation of Inflammatory Molecules in Children With Cerebral Palsy.

AIM: To evaluate the effects of systematic rehabilitation on both the neuropsychomotor development, and on the peripheral response from immunological and neuroplastic mediators in children with cerebral palsy. METHODS: This is a prospective cohort study with 90 children with cerebral palsy at 18 months of age. Sixty children received rehabilitation for 6 months, and they were compared to 30 children that were placed in the waiting list. Peripheral biomarkers and neuropsychomotor parameters were compared between the Rehab vs the Nonrehab groups at baseline and at 6 months. RESULTS: Results showed higher Bayley III scores in the Rehab group, with significant differences in inflammatory and neurotrophic biomarkers between groups. Rehabilitation was associated to decreased levels of IL-12p70, IL-6, IL-1ß, CXCL8 IL-8, and CXCL9/MIG and increased levels of BDNF and GDNF. Nonrehab children had stable immune molecule levels but decreased BDNF levels over time. CONCLUSION: Rehabilitation improved neurodevelopment parameters and modulated levels of inflammatory (↓) and neurotrophic (↑) biomarkers.

Assessment of Biochemical, Inflammatory Biomarkers and Ultra-Processed Food Consumption in Children with Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study.

OBJECTIVE: This study evaluated anthropometric, biochemical, and inflammatory biomarkers, as well as dietary intake in Brazilian children diagnosed with small intestinal bacterial overgrowth (SIBO) and compared them with their counterparts without SIBO. METHODS: This was a cross-sectional study with 106 children aged 7 to 10 years. A glucose-hydrogen breath test was performed to diagnose small intestinal bacterial overgrowth (SIBO). Anthropometric and dietary characteristics were assessed. Blood samples were collected and serum biochemical parameters and cytokines were measured. RESULTS: The occurrence of SIBO was 13.2%. Age, BMI, BMI/age WC, BFP, sex and biochemical markers were similar between SIBO-positive and SIBO-negative children (p > 0.05). High consumption of ultra-processed foods tended to be higher in SIBO-positive compared to SIBO-negative children (47.8 ± 8.2 vs. 42.6 ± 9.5, p = 0.06). Serum levels of IL-17 were higher in SIBO-positive than in SIBO-negative children [69.5 (5.4-125.7) vs. 53.4 (2.3-157.7), p = 0.03], while serum levels of IL-10 were lower in SIBO-positive than in SIBO-negative children [2.3 (0.6-7.2) vs. 5.7 (0.5-30.8), p = 0.04]. Finally, in a logistic regression adjusted for sex, BMI and age, consumption of ultra-processed foods (p = 0.03) and IL-6 levels (p = 0.003) were found to contribute to the occurrence of SIBO. CONCLUSION: this study identified for the first time an occurrence of 13% of SIBO in children living in the northeastern region of Brazil and showed that consumption of ultra-processed foods and serum levels of IL-6 may influence the occurrence of the SIBO in the pediatrics population.

Unraveling the Interaction between Inflammation and the Cardiometabolic Index in Older Men: A Pilot Study.

Both cardiometabolic and chronic inflammatory diseases pose a significant challenge to global public health, particularly among older adults. Here, we investigated the interplay between systemic inflammatory status and the cardiometabolic index (CMI) in older men with adequate weight or obesity. In this observational cross-sectional study, older men (71.79 ± 7.35 years) were separated into groups with normal weight (NW, n = 34) and obesity (O, n = 32) to assess circulating levels of pro- and anti-inflammatory cytokines and CMI. Overall, the O group showed not only a higher inflammatory status but also increased CMI (p < 0.0001) compared with the NW group. Interestingly, only positive correlations were found between pro- and anti-inflammatory cytokines in both groups. Through multivariate regression analysis, IL-6 (ß = -0.2276, p = 0.0003) and IL-10 (ß = 0.2023, p = 0.0030) significantly influenced CMI in the NW group. No significant results were found in the O group. Our findings reinforce the effects of obesity in inflammaging, as well as suggesting that the influence of cytokines in CMI occurs in older men with normal weight, since the elevated pro-inflammatory profile observed in older men with obesity can interfere in this effect.

Genetic, Clinical, Epidemiological, and Immunological Profiling of IgG Response Duration after SARS-CoV-2 Infection.

The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.

Levels of Plasma Endothelin-1, Circulating Endothelial Cells, Endothelial Progenitor Cells, and Cytokines after Cardiopulmonary Bypass in Children with Congenital Heart Disease: Role of Endothelin-1 Regulation.

Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children's peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Ɲ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Ɲ-CECs increased in both CHD groups and that Ɲ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD.

Mid-pregnancy circulating cytokine levels, placental efficiency and their relationship with preterm birth.

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1ß, TNFß, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.