Diagnostic value of cytokines in severe childhood Mycoplasma pneumoniae pneumonia combined with Adenovirus infection.

BACKGROUND: To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV). METHODS: The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves. RESULTS: There was no difference between group A1 and group A2, group B1 and group B2 in terms of age, gender, duration of hospitalisation and fever. The levels of calcitoninogen(PCT), lactate dehydrogenase concentration(LDH), interleukin(IL)-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ in group A were higher than group B. The severe group (A1, B1) was significantly higher than the mild group (A2, B2) in terms of D-dimer, CRP, PCT, LDH, IL-6, IL-8, IL-10, IL-17a and number of patients with pleural effusion, solid lung changes. Among the individual indexes of D-dimer, CRP, N%,LDH, and PCT, the AUC of the combined test was 0.977, which was higher than that of the individual indicators. Among IL-6, IL-8, IL-10, and IL-17a, the AUC of the combined assay was 0.802, which was higher than that of the individual indicators. CONCLUSION: MP combined with ADV infection was associated with increased expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, IFN-γ, and LDH. IL-6, IL-8, IL-10, IL-17a, LDH, PCT, CRP, and D-dimer could be used as predictors of SMPP and the combined test can improve the diagnostic value.

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial.

BACKGROUND: Inflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients. METHODS: This study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines. RESULTS: During the study's follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1ß, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients. CONCLUSION: AD-MSCs represent a potential intervention to prevent age-related inflammation in patients. TRIAL REGISTRATION: ClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020.

Protective Effect of Perilla Seed Meal and Perilla Seed Extract against Dextran Sulfate Sodium-Induced Ulcerative Colitis through Suppressing Inflammatory Cytokines in Mice.

An excessive inflammatory response of the gastrointestinal tract is recognized as one of the major contributors to ulcerative colitis (UC). Despite this, effective preventive approaches for UC remain limited. Rosmarinic acid (RA), an enriched fraction from Perilla frutescens, has been shown to exert beneficial effects on disease-related inflammatory disorders. However, RA-enriched perilla seed meal (RAPSM) and perilla seed (RAPS) extracts have not been investigated in dextran sulfate sodium (DSS)-induced UC in mice. RAPSM and RAPS were extracted using the solvent-partitioning method and analyzed with high-pressure liquid chromatography (HPLC). Mice with UC induced using 2.5% DSS for 7 days were pretreated with RAPSM and RAPS (50, 250, 500 mg/kg). Then, the clinical manifestation, colonic histopathology, and serum proinflammatory cytokines were determined. Indeed, DSS-induced UC mice exhibited colonic pathological defects including an impaired colon structure, colon length shortening, and increased serum proinflammatory cytokines. However, RAPSM and RAPS had a protective effect at all doses by attenuating colonic pathology in DSS-induced UC mice, potentially through the suppression of proinflammatory cytokines. Concentrations of 50 mg/kg of RAPSM and RAPS were sufficient to achieve a beneficial effect in UC mice. This suggests that RAPSM and RAPS have a preventive effect against DSS-induced UC, potentially through alleviating inflammatory responses and relieving severe inflammation in the colon.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Introduction: Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. Methods: This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. Results: No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Conclusion: Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Clinical value of BRE-AS1 in myocardial infarction and its role in myocardial infarction-induced cardiac muscle cell apoptosis.

Objectives. The aim of this study was to investigate the expression of long non-coding RNA (lncRNA) brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in patients with acute myocardial infarction (AMI) and its effect on ischemia/reperfusion (I/R)-induced oxidative stress and apoptosis of cardiomyocytes. Methods. Serum BRE-AS1 levels in patients with AMI was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic values of BRE-AS1 were evaluated. H9c2 cells were treated with hypoxia/reoxygenation to establish an in vitro myocardial infarction cell model. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined by commercial kits. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the cell viability and cell apoptosis. Results. The expression of BRE-AS1 in serum of patients with AMI is upregulated, which shows the clinical diagnostic value for AMI. In the I/R injury cell model, the knockout of BRE-AS1 can significantly alleviate the increase in TNF-α, IL-1ß, and IL-6 levels, inhibit the production of LDH and MDA, increase the activities of SOD and GSH-Px, promote the cell viability and suppress cell apoptosis. Conclusions. Abnormally elevated BRE-AS1 has a high diagnostic value for AMI as well as a prognostic value for major adverse cardiovascular events (MACEs). The elevation of BRE-AS1 promoted oxidative stress injury and cell apoptosis in vitro.

Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population.

Background: Extensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship. Results: The forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD. Conclusion: This MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1ß, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-ß (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs). METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines. RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1ß [standardized mean difference (SMD) = -1.94, 95% confidence interval (CI) (-2.99, -0.90), P = 0.0003], IL-6 [SMD = -1.65, 95% CI (-2.33, -0.97,) P < 0.000 01], IL-17 [SMD = -2.41, 95% CI (-3.61, -1.20), P < 0.0001], tumor necrosis factor (TNF)-α [SMD = -1.84, 95% CI (-2.61, -1.06), P < 0.0001], and interferon (IFN)-γ [SMD = -1.54, 95% CI (-2.43, -0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI (0.15, 2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI (1.39, 2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD = -0.63, 95% CI (-1.82, 0.57), P = 0.30]. CONCLUTIONS: Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Effect of cytokines on advanced hepatocellular carcinoma prognosis receiving radiotherapy and tislelizumab plus anlotinib: a single-center phase II clinical trial.

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.

Myokine Secretion following an Aerobic Exercise Intervention in Individuals with Type 2 Diabetes with or without Exercise Resistance.

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.

Effects of Bioactive Dietary Components on Changes in Lipid and Liver Parameters in Women after Bariatric Surgery and Procedures.

Excess adipose tissue, as well as its distribution, correlates strongly with disorders of lipid and liver parameters and chronic inflammation. The pathophysiology of metabolic diseases caused by obesity is associated with the dysfunction of visceral adipose tissue. Effective and alternative interventions such as the Bioenteric Intragastric Balloon and bariatric surgeries such as the Roux-en-Y gastric bypass. The aim of this study was to assess the effect of modifying the recommended standard weight loss diet after bariatric surgery and procedures on reducing chronic inflammation in overweight patients. In the study, bioactive anti-inflammatory dietary components were used supportively. Changes in the concentrations of lipid parameters, liver parameters, antioxidant enzymes, cytokines, and chemokines were demonstrated. The enrichment of the diet, after bariatric surgery, with the addition of n-3 EFAs(Essential Fatty Acids), bioflavonoids, vitamins, and synbiotics resulted in higher weight losses in the patients in the study with a simultaneous reduction in parameters indicating liver dysfunction.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1ß (interleukin 1ß), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1ß levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.

HIV-infected (HIV+) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV+ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1ß, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV+ individuals than healthy controls. Increasing CD4 T cell counts in the HIV+ cohort did not significantly change the circulating cytokine levels, although levels of IL-1ß increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV+ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV+ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1ß and IL-17 were slightly elevated. Furthermore, increasing age of the HIV+ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV+ individuals had higher levels of TNF-α, IFN-γ, and IL-1ß. In summary, our findings show that HIV+ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.

Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial.

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration.Registration: ClinicalTrials.gov NCT04443673, 23/06/2020.

The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review.

OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. RESULTS: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). CONCLUSION: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

Killer Function of Circulating Neutrophils in Relation to Cytokines in Uterine Myoma and Endometrial Cancer.

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).

The role of M1/M2 macrophage polarization in primary Sjogren's syndrome.

BACKGROUND: The purpose of this study was to investigate the role of macrophage polarization in the pathogenesis of primary Sjogren's syndrome (pSS). METHODS: Peripheral venous blood samples were collected from 30 patients with pSS and 30 healthy controls. Minor salivary gland samples were abtainted from 10 of these patients and 10 non-pSS controls whose minor salivary gland didn't fulfill the classification criteria for pSS. Enzyme-linked immuno sorbent assay was used to examine the serum concentration of M1/M2 macrophage related cytokines (TNF-a, IL-6, IL-23, IL-4, IL-10 and TGF-ß). Flow cytometry was used to examine the numbers of CD86+ M1 macrophages and CD206+ M2 macrophages in peripheral blood mononuclear cells (PBMCs). Immunofluorescence was used to test the infiltration of macrophages in minor salivary glands. RESULTS: This study observed a significant increase in pSS patients both in the numbers of M1 macrophages in peripheral blood and serum levels of M1-related pro-inflammatory cytokines (IL-6, IL-23 and TNF-α). Conversely, M2 macrophages were downregulated in the peripheral blood of pSS patients. Similarly, in the minor salivary glands of pSS patients, the expression of M1 macrophages was increased, and that of M2 macrophages was decreased. Furthermore, a significantly positive correlation was found between the proportions of M1 macrophages in PBMCs and serum levels of IgG and RF. CONCLUSIONS: This study reveals the presence of an significant imbalance in M1/M2 macrophages in pSS patients. The M1 polarization of macrophages may play an central role in the pathogenesis of pSS.