IL-1ra Levels Research Articles

The role of plasma inflammatory markers in late-life depression and conversion to dementia: a 3-year follow-up study.

Late-life depression (LLD) has been linked to increased likelihood of dementia, although mechanisms responsible for this association remain largely unknown. One feature frequently observed in both LLD and dementia is elevated levels of plasma inflammatory markers. The present study aimed to compare the levels of 12 plasma inflammatory markers between older people with LLD and controls, and to explore whether these markers, along with clinical characteristics, can predict dementia in patients with LLD within 3 years of follow-up. Using multiple linear regression with stepwise adjustment, we compared levels of plasma inflammatory markers (IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4) between 136 inpatients with LLD (PRODE cohort) and 103 cognitively healthy non-depressed controls (COGNORM cohort). In the PRODE cohort, follow-up data was available for 139 patients (of them 123 had data on baseline plasma inflammatory markers); 36 (25.9%) developed dementia by Year 3 (n = 31 for those with cytokine data). Using Cox proportional hazards regression, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, treatment response, number of episodes) predicted progression to dementia during follow-up. Levels of IL-1ra, CCL-2, CCL-4, IFN-γ and IL-17a were significantly higher in LLD patients compared to controls in the majority of models. However, none of the inflammatory markers predicted progression from LLD to dementia in the PRODE cohort. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia.

Analysis of intracranial lesions in patients with HIV-associated cryptococcal meningitis

BackgroundIntracranial imaging abnormalities are commonly observed in patients suffering from HIV-associated cryptococcal meningitis, both before and during the treatment period. This study aims to analyze the prevalence, origins, radiological characteristics, treatments, and prognosis of intracranial lesions in patients with HIV-associated cryptococcal meningitis, thereby providing references for future clinical decision-making.MethodsThe clinical data of patients diagnosed with HIV-associated cryptococcal meningitis and admitted to the Shanghai Public Health Clinical Centre between 2013 and 2019 were collected. Logistic regression analysis was subsequently conducted to identify potential risk factors associated with the development of intracranial lesions in this patient group.ResultsOf 211 patients analyzed, 64.5% (136/211) had intracranial lesions during treatment and follow-up. Initial cranial imaging showed 60% had lesions pre-treatment. Throughout treatment, 32.7% (52/159) developed new or worsened lesions. Mortality rates at 2 weeks, 8 weeks, and 2 years for those with detected lesions were 3%, 7.6%, and 13.2%, respectively. Lesions were primarily caused by Cryptococcus (70.5%) and Mycobacterium (24.3%). Lacunar infarcts, especially in the basal ganglia, were the most common type. Patients aged 50 years or older, and those presenting with altered mental status upon admission, were found to be more likely to have intracranial lesions at baseline, with adjusted odds ratios of 5.364 (95% CI: 1.468-19.591, P=0.011) and 7.970 (95% CI: 2.241-28.337, P=0.001), respectively. Patients with lesion progression showed higher levels of IFN-γ, IL-4, IL-5, IL-6, IL-1Ra, IL-1β, GM-CSF, Eotaxin, and Basic FGF in cerebrospinal fluid after four weeks of treatment.ConclusionIntracranial lesions in HIV-associated cryptococcal meningitis patients are mostly due to Cryptococcus and Mycobacterium infections. They often appear as lacunar infarcts, predominantly in the basal ganglia, and can worsen with treatment initiation, possibly due to higher baseline cytokine levels in cerebrospinal fluid.

Predictive and diagnostic biomarkers for cytomegalovirus infection in patients with rheumatic musculoskeletal diseases treated by high-dose glucocorticoid therapy: multicentre, prospective cohort study.

The incidence of cytomegalovirus (CMV) infection or disease in patients with rheumatic musculoskeletal diseases is reported to be 2%. Over half received pulsed methylprednisolone, and some experienced a fatal outcome. In this study, we aimed to explore predictive and diagnostic biomarkers for CMV infection or disease in such patients and compare them with biomarkers reported for immune reconstitution inflammatory syndrome (IRIS) in people with HIV. In this multicentre prospective cohort study, we collected blood and saliva samples from 38 patients with rheumatic musculoskeletal disease before initiating high-dose glucocorticoid therapy, at the start of glucocorticoid tapering, at the onset of CMV infection, and 4 weeks later. Peripheral blood cell counts, flow cytometry for CD4, CD8, and Tregs, ELISA for cytokine/chemokine panels, and measurements of herpesvirus-derived DNA in saliva were performed. Lower white blood cells, CD4+ cells, IL-6, and interferon-γ levels and higher interferon-inducible protein (IP)-10 and granulysin levels at baseline could be predictive biomarkers for CMV infection. Furthermore, lower platelet counts and higher IL-10, IP-10, granulysin, TNF-a, IL-1ra, and IL-15 levels at the onset of CMV infection were found as diagnostic biomarkers for CMV infection. EBV, human herpes virus (HHV)-6, and HHV-7 DNA levels in the saliva were significantly increased after high-dose glucocorticoids, regardless of CMV infection. We identified predictive and diagnostic biomarkers for CMV infection after high-dose glucocorticoid therapy for rheumatic musculoskeletal diseases. While similarities with IRIS biomarkers in patients living with HIV were observed, complete agreement could not be confirmed.

Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils

Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B. abortus infects and replicates within murine omental macrophages. Throughout the chronic phase of infection, the omentum accumulates macrophages, monocytes and neutrophils. The maintenance of PD-L1+Sca-1+ macrophages, monocytes and neutrophils in the omentum depends on the wadC-encoded determinant of Brucella LPS. We demonstrate that PD-L1+Sca-1+ murine omental neutrophils produce high levels of IL-1RA leading to T cell hyporesponsiveness. These findings corroborate brucellosis patient analysis of whole blood displaying upregulation of PDL1 and Ly6E genes, and of serum exhibiting high levels of IL-1RA. Overall, the omentum, a reservoir for B. abortus, promotes bacterial persistence and causes CD4+ and CD8+ T cell immunosuppression by IL-1RA secreted by PD-L1+Sca-1+ neutrophils.

Diagnostic Markers of Severe COVID-19 and Community-Acquired Pneumonia in Children From Southern India.

COVID-19 severely impacts children in India, with many developing severe pneumonia or multisystem inflammatory syndrome (MIS-C). Concurrently, non-COVID-19 respiratory viruses causing community-acquired pneumonia (CAP) have resurged. These conditions present similarly, challenging accurate diagnosis. This study aims to compare inflammatory markers and clinical parameters in children with severe COVID-19 pneumonia, non-COVID-19 CAP, and COVID-associated MIS-C. We assessed 12 mediators in serum from 14 children with severe COVID-19 pneumonia, 16 with severe non-COVID-19 CAP, and 9 with MIS-C. Clinical characteristics and routine laboratory findings at admission were recorded. Children with MIS-C had significantly higher levels of IL-1RA, IL-8, and TNF compared with those with severe COVID-19 pneumonia; and higher levels of CCL2, HGF, M-CSF, and IL-8 compared with severe non-COVID-19 CAP. GROα levels tended to be higher in severe COVID-19 pneumonia. Clinical presentations were similar, but MIS-C patients had distinct laboratory findings, including lower platelet counts and albumin levels, and higher creatinine and liver enzyme levels. MIS-C exhibited a unique inflammatory profile. IL-8 emerged as a potential biomarker for MIS-C, while increased GROα levels in severe COVID-19 pneumonia merit further exploration. Combining inflammatory markers with routine laboratory parameters may improve the diagnosis and differentiation of these conditions, enhancing patient management.

Assessment of the Utility of Selected Inflammatory Markers in Correlation with Magnetic Resonance Enterography (MRE) Findings in the Diagnosis of Crohn's Disease.

Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. The search continues for new markers for assessing the activity of CD. Among them, pro-inflammatory and anti-inflammatory cytokines appear promising. We performed the analysis of cytokine concentrations in blood serum using the Bio-Plex Multiplex system (Bio-Rad), and their correlations with radiological parameters were assessed by magnetic resonance enterography (MRE), and fecal calprotectin levels were measured quantitatively by ELISA and clinical evaluation according to the Crohn's Disease Activity Index (CDAI). Our study found that measuring cytokine serum concentrations can be a valuable tool in the diagnosis and treatment of CD. Positive correlations were reported between contrast enhancement on DCE-MRE and the concentrations of PDGF-BB and RANTES. Also, a positive correlation was found between the delayed-phase of DCE and IL-10 concentration, a strong negative correlation between the delayed-phase of DCE and IL-12 concentration, and a strong positive correlation between the delayed-phase of DCE and RANTES concentrations. A strong positive correlation was also observed between the thickness of the intestinal wall on T2-weighted images and RANTES concentration. Therefore, concentrations of PDGF-BB, RANTES, IL-10 and IL-12 are promising markers of CD activity. The study also demonstrated significant correlations between the severity of disease activity assessed by the CDAI and the concentrations of IL-5, IL-8 and IL-9, as well as positive correlations between the levels of fecal calprotectin and the concentrations of IL-1RA and VEGF. Therefore, the levels of IL-5, IL-8, IL-9, VEGF and IL-1RA may be useful markers in the diagnosis and clinical assessment of disease activity.

A Clinical Study to Evaluate the Anti-inflammatory Effect of Lactoferrin + Disodium Guanosine Monophosphate Therapy in the Patients with Chronic Kidney Disease.

India is impacted by the increasing burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD), necessitating efficient management and therapy. CKD is characterized by elevated levels of inflammatory biomarkers, specifically IL-1β, IL-1RA, IL-6, TNF-α, TGF-β, and fibrinogen. The aim of this research is to determine the antiinflammatory effects of lactoferrin + disodium guanosine monophosphate therapy in CKD patients. The objective of this study is to examine the efficacy of this therapy versus conservative CKD management alone in reducing inflammation. This study intends to examine the possible benefits of study drug in treating inflammation associated with CKD by analyzing its effect on inflammatory markers including IL-6 and TNF-α. This randomized, open-label, parallel group, two-arm clinical study, comprising of 40 patients with CKD, with 20 patients in each group. The groups were well-matched in terms of demographic characteristics. Conception, screening, randomization, and follow-up visits including physical examinations, laboratory investigations, and medication dispensation were all carried out over a 29-week period. Creatinine clearance, estimated glomerular filtration rate (eGFR), estimated urine urea nitrogen, and inflammatory markers (IL-6, IL-10, TNF-α, CRP) were analyzed at time of screening and at 3 and 6-month postrandomization. The study found a significant decrease in inflammatory markers, including TNF-α, IL-6, and IL-10, in the group receiving study drug, indicating its potential as an antiinflammatory intervention for managing CKD. Secondary endpoints, including hemoglobin (Hb) and e-GFR levels, showed nonsignificant improvements in the study group compared to the control group. No significant adverse events were reported during the study. The study highlights the potential antiinflammatory effects of the lactoferrin + disodium guanosine monophosphate therapy in individuals with CKD. The findings suggest that study drug may be a viable intervention for managing inflammation in CKD patients. Further research is needed to validate these results and explore its long-term effects in CKD management.

MARKERS OF INFLAMMATION ARE MODIFIED BY SEX, FRAILTY AND EXERCISE IN A HEAD-DOWN TILT BEDREST STUDY

Abstract Prolonged bedrest can induce physiological stress thereby exacerbating frailty and inflammation. We explored whether Head-Down Tilt (HDT) bedrest with or without exercise would alter inflammatory markers implicated in frailty. Twenty 55-65-year-old males (baseline frailty index (FI)=0.02±0.02) and females (FI=0.03±0.03) were subjected to HDT bedrest (2-weeks). Half were randomly assigned to a high-intensity interval/aerobic/strength training exercise intervention for 60 minutes/day (Control: n=4 males, 5 females; Exercise n=5 males, 6 females). FI and serum inflammatory cytokines were measured (multiplex assay) during bedrest (days 0,1,3,7,14), and recovery (days 0,4,32). Data were analyzed with linear mixed models. Proinflammatory marker levels (interleukin (IL)-6, IL-8) increased during bedrest in all groups but were higher in males than females (IL-6: ß=8.87, IL-8: ß=12.93; p< 0.01). IL-8 declined during recovery in all groups, although IL-8 and IL-6 remained higher in males (IL-6: ß=9.32, IL-8: ß=2.85, p< 0.01). The anti-inflammatory cytokine IL-10 was higher in males than females during bedrest, declined in recovery and remained highest in males. During bedrest proinflammatory cytokines (IL-1ß, IL-12) increased as frailty increased in all participants (IL- ß: ß=0.01, IL-12: ß=0.02, p< 0.05) whereas monocyte chemoattractant protein-1 levels declined (ß =-20.54, p< 0.05). The anti-inflammatory protein IL-1ra increased with frailty throughout bedrest in all, especially those who exercised (ß=3.15, p< 0.01). In older adults, inflammatory markers increased during bedrest, declined during recovery and were higher in males than females. Some inflammatory markers increased in parallel with frailty during bedrest. Exercise also increased IL-1ra levels, which may help reduce inflammation in older adults during prolonged bedrest.

Maternal characteristics are associated with human milk anti-inflammatory proteins in two populations

Milk anti-inflammatory compounds are ubiquitous in milk but vary greatly within and between populations. The causes of this variation and how this variation impacts infant phenotype is not well-characterized. The goal of this study was to explain how maternal characteristics across two disparate populations impact the levels of TGF-β2 and IL-1ra in human milk. Two populations of mothers, one from rural Kenya and the other from urban U.S., were queried about months since birth, age, sex of infant, height, BMI, triceps skinfold, parity, post-birth resumption of menstrual period, and exclusive breastfeeding. Mothers’ foremilk was assayed for TGF-β2 and IL-1ra as well as % milk fat. Mixed models were used to measure the relationships between maternal characteristics and milk biomarkers, adjusting for population. Statistically significant maternal characteristics were then used to develop path models incorporating infant phenotype. Path results indicated that maternal height and months postpartum significantly predicted milk TGF-β2, which then significantly predicted infant height-for-age. Exclusive breastfeeding and milk fat percent predicted IL-1ra, which was not related to infant weight-for-age. These results have implications for understanding the intergenerational effect of maternal context on infant phenotype via biomarkers in human milk.

Obesity Is Associated With Higher Levels of Circulating Cytokines Involved in the Development of Cardiovascular Disease in People Living With HIV.

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterized. We aimed to analyze the difference in circulating cytokines involved in pathways associated with comorbidities in PLWH according to the presence or absence of obesity. Age- and sex-matched PLWH with and without obesity (body mass index ≥30 kg/m 2 ) from a multicenter, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (high sensitivity C-Reactive Protein [hsCRP], interleukin (IL)-2, IL-6, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, tumor necrosis factor-alpha, interferon-gamma, IL-18), coagulation (von Willebrand Factor [vWF], D-dimer, soluble CD40 ligand), endothelial function (E-selectin, P-selectin, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1), atherosclerosis (myeloperoxidase [MPO], lipoprotein-associated phospholipase A2), immune regulation (IL-1 receptor antagonist [IL-1RA]), innate immune activation (macrophage inflammatory protein-1, monocyte chemoattractant protein-1, soluble CD163, soluble CD14), and microbial translocation (lipopolysaccharide binding protein) were measured in the 2 groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, sex, ethnicity, smoking status, and antiretroviral therapy. Ninety-nine antiretroviral therapy-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and lipopolysaccharide binding protein. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation, and atherosclerosis pathways, were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (adjusted odds ratio 2.7, 95% CI: [1.7 to 4.29]), IL-6 (3.77 [1.43-9.93]), vWF (5.33 [1.51-18.75]), E-selectin (6.28 [1.36-29.04]), MPO (6.85 [1.87-25.04]), and IL-1RA (6.45 [2.28-18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation. Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis, and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point toward an unfavorable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Prognostic performance of early immune and endothelial activation markers in mild-to-moderate COVID-19 outpatients: a nested case-control study.

Evidence on the association of biomarkers of host response to infection with COVID-19 clinical outcomes has focused mainly on hospitalized patients. We investigated the prognostic performance of 39 immune and endothelial activation markers measured early in the course of disease to predict the development of severe COVID-19 and hospitalization. We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment. A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19. Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions.

Chemopreventative potential of Salsola tuberculatiformis Botch and Compound A in the differential regulation of IL-1Ra:IL-1α in UVB exposed skin keratinocytes

BackgroundSalsola tuberculatiformis Botsch, commonly known as Gannabos, is a Namibian shrub known for its contraceptive properties in rats and its ability to modulate adrenal steroidogenesis both in vitro and in vivo. Due to the labile nature of the active compounds in the shrub, a more stable synthetic analogue, Compound A, was synthesized. This compound has demonstrated similar contraceptive and steroidogenic properties as the original extract from S. tuberculatiformis. Additionally, Compound A has shown potent anti-inflammatory and anti-cancer effects in skin, raising the question of whether the S. tuberculatiformis extract might exhibit similar properties. PurposeThe study aimed to evaluate the anti-inflammatory and anti-carcinogenic properties of S. tuberculatiformis extract and Compound A, particularly their effects on UVB-induced inflammation, cell growth parameters, and oxidative status in HaCaT cells. MethodsThe biological activity of S. tuberculatiformis extract and Compound A was assessed using a cytochrome P450 assay. Anti/pro-inflammatory effects were evaluated by measuring IL-1α and IL-1Ra production using an ELISA assay. Additionally, the study monitored cell viability through ATP production, apoptosis via Caspase-3 activity, and oxidative stress using the DCFDA assay. ResultsS. tuberculatiformis extract inhibited IL-1α production at lower concentrations while increasing IL-1Ra at higher concentrations. This was associated with reduced cell viability and increased pro-oxidant (ROS) and pro-inflammatory activity (intracellular IL-1α). Compound A, on the other hand, reduced IL-1Ra and IL-1α levels by inducing apoptosis. However, at higher concentrations, Compound A significantly increased extracellular IL-1Ra levels and enhanced pro-apoptotic and pro-oxidant activity. The extract exhibited different anti-inflammatory effects compared to Compound A, as evidenced by the increased intracellular IL-1Ra: IL-1α ratio. ConclusionThe data suggest that S. tuberculatiformis acts as an anti-inflammatory agent at low concentrations by inhibiting intracellular IL-1α production, while at higher concentrations, it regulates pro-inflammatory signaling through IL-1Ra. These anti/pro-inflammatory effects may have potential relevance in wound healing. Compound A displayed a novel indirect anti-inflammatory effect by removing inflamed and damaged cells via apoptosis and ROS production. The pro-oxidant activity of Compound A, potentially due to aziridine formation, appears to accelerate the progression of damaged cells into apoptosis.

Serum proteomics identifies biomarkers for predicting non-survivors in elderly COVID-19 patients

In December 2022, China ceased the zero-COVID-19 policy, resulting in an increase in hospitalizations and deaths due to COVID-19, particularly among the elderly population. Predicting non-survivors aims to identify high-risk patients and enable targeted interventions to improve survival rates. Additionally, understanding factors affecting prognosis provides essential insights for further research and optimization of treatment strategies. We applied 4D-DIA mass spectrometry for serum proteome analysis and provided a comprehensive characterization of disease features in elderly patients within the Chinese population. Our study elucidated that immune disorders, lung damage, and cardiovascular disorders are predominant causes of death in these patients. Compared to clinical indices, proteomic analysis is more sensitive in tracing these disorders. We also provided a prediction panel for survival outcomes of elderly patients using levels of CXCL10, CXCL16 and IL1RA, which were validated by ELISA. These biomarkers will help improve predictive efficacy for survival outcomes in elderly patients.

Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study.

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC.

In Vitro Anti-inflammatory Effect of Secretome from Umbilical Cord-derived Mesenchymal Stem Cells in COVID-19 Patient Blood: A Study on sIL-6R, sgp130, IL-1RA and Anti/pro Inflammatory Cytokines

COVID-19 exhibits a wide range of clinical manifestations which severity of the disease is linked to uncontrolled escalation of inflammatory mediators. Ongoing research has identified the immunomodulatory effects of the MSC-derived secretome as a potential therapy for COVID-19. However, the precise mechanism by which the secretome exerts its therapeutic effect on COVID-19 remains unclear. This study aims to investigate whether the components of the UC-MSC-derived secretome can alter the inflammatory characteristics of immune cells. To achieve this, an in vitro study will be conducted involving co-incubation of whole blood with secretomes, followed by LPS stimulation. A total of 12 blood samples from severe COVID-19 and healthy subjects were cultured into three groups (RPMI control, 3μl and 9μl secretome group) incubated for 24 hours. Then, the cultures were exposed to LPS for 48 hours. The levels of sIL-6R, sgp130, IL-1RA, IL-6, TNF-α, IFN-γ, and IL-10 were measured. Results showed that LPS increased IL-6, TNF-α, and IL-10 production, while reducing sIL-6R, and sgp130, but no changes seen in IFN-γ in secretome-incubated blood cultures. The post-LPS/pre-LPS ratio analysis was conducted to investigate the anti-inflammatory potential of secretome. It was found that the secretome provides its anti-inflammatory effects through the role of IL-1RA.

Fluctuation trend of inflammatory indexes related to gestational diabetes mellitus from second trimester to third trimester of pregnancy

ObjectiveThis study aims to assess the prognostic and diagnostic value of inflammatory indexes related to gestational diabetes mellitus (GDM) from the second trimester to the third trimester of pregnancy.Materials and methodsIn this study, we randomly selected 65 pregnant women diagnosed with GDM at our hospital from December 2022 to June 2023 to form the GDM group (n = 65). Additionally, 65 pregnant women at the same gestational weeks without GDM were selected as the Normal group (n = 65). We collected gestational information and serum samples at 24 and 36 weeks of gestation from the participants. The levels of NLRP3, IL-1Ra, and TBP-2 were determined using enzyme-linked immunosorbent assay (ELISA) to explore their changes during pregnancy. Further, this study analyzed the changes in the levels of NLRP3, IL-1Ra, and TBP-2 at 24 and 36 weeks of gestation in GDM patients and their correlation with gestational diabetes mellitus.ResultsThe study showed that pre-pregnancy body mass index (BMI), neonatal weight, gestational hypertension, and macrosomia are significantly associated with the occurrence of GDM (P < 0.05). Statistical analysis comparing the normal and GDM groups found no significant changes in the levels of NLRP3, IL-1Ra, and TBP-2 with the progression of gestation in the normal group. In contrast, in the GDM group, the levels of IL-1Ra in serum samples at 24 and 36 weeks were significantly increased (P < 0.05) while the levels of NLRP3 and TBP-2 were significantly reduced (P < 0.05). At 36 weeks, there was a positive correlation between the levels of NLRP3, IL-1Ra, and TBP-2. Compared to the normal group, the overall levels of NLRP3, IL-1Ra, and TBP-2 in the GDM group were lower (P < 0.05) and the weight of the newborns was significantly correlated with these three indicators (P < 0.05), specifically newborn weight increased with the levels of NLRP3 and TBP-2 but decreased with the increase of IL-1Ra (P < 0.05). Multifactorial logistic regression analysis further revealed that NLRP3 is an independent factor influencing GDM (P < 0.05). ROC curve analysis of the NLRP3 level at 24 weeks of gestation found that NLRP3 has a good value in predicting GDM (AUC = 0.720, 95%CI 0.630–0.809, P < 0.001) and the combined prediction of NLRP3, IL-1Ra, and TBP-2 also showed a good predictive value for GDM.ConclusionThe changes in NLRP3, IL-1Ra, and TBP-2 persisted throughout the 24 to 36 weeks of gestation, playing an important role in predicting the occurrence of GDM and the weight of the newborn.

Systemic Inflammation In Asymptomatic Hyperuricemia With Sonographic Crystal Deposits, Including A Comparison With Normouricemia And Gout.

To describe the inflammatory profile of asymptomatic hyperuricemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout, and normouricemia. Based on serum urate levels, musculoskeletal ultrasound, and history of flares, we divided 122 participants into four groups: normouricemia, AH-MSUneg, AH-MSUpos, and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2-3 (G2-3) double contour and/or tophi, G1-3 double contour and/or tophi, G1-3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint), and G2-3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates, and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricemics. Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-β, and galectin-3 were higher in hyperuricemics vs normouricemics. Sex, obesity, and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUpos vs AH-MSUneg groups, except for higher calprotectin using G1-3 sonographic definitions and higher CRP and TGF-β when restricted to women and obese participants. Hyperuricemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-β. Sex, obesity, and comorbidities influenced some inflammatory responses.

Gut Microbiota and Cytokine Profile in Cirrhosis.

Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them. In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing. Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus. The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

Mitigation of ultraviolet-induced erythema and inflammation by para-hydroxycinnamic acid in human skin.

To evaluate whether p-hydroxycinnamic acid (pHCA) alone and in combination with niacinamide (Nam) can mitigate UV-induced erythema, barrier disruption, and inflammation. Three independent placebo-controlled double-blinded studies were conducted on female panellists who were pretreated on sites on their backs for 2 weeks with skin care formulations which contained 0.3% or 1% pHCA with 5% Nam, 1% pHCA alone, 1.8% octinoxate, or control formula. Treated sites were then exposed to 1.5 minimal erythemal dose (MED) solar simulated radiation (SSR) and had chromameter and expert grading measures for erythema, barrier integrity via TEWL, and the skin surface IL-1RA/IL-1α inflammatory biomarkers isolated from D-Squame tapes. Across the three independent studies, pHCA alone or in combination with Nam showed a significant mitigation of UV-induced erythema, barrier disruption, and levels of the surface inflammatory biomarkers IL-1RA/IL-1α. The cinnamate analogue Octinoxate did not replicate the effects of pHCA. The study results show that pHCA alone or in combination with Nam can mitigate UV-induced damage to skin. These include mitigation of UV-induced erythema as measured by instrument and expert grade visualization. Additionally, pHCA with Nam protected damage to the barrier and reduced the induction of the SASP-related surface inflammatory biomarker IL-1RA/IL-1α. The inability of Octinoxate to have any protective effect and the detection of low levels of pHCA on skin surface after 24 h of application supports that these effects are based on a biological response to pHCA. These findings add to the body of evidence that pHCA alone or in combination with Nam can enhance the skin's biological response to UV-induced damage. This supports pHCA can potentially impact aging and senescence, thereby maintain skin's functionality and appearance.

Circulating inflammatory cytokines and the risk of sepsis: a bidirectional mendelian randomization analysis

BackgroundSepsis is a life-threatening condition that is characterized by multiorgan dysfunction and caused by dysregulated cytokine networks, which are closely associated with sepsis progression and outcomes. However, currently available treatment strategies that target cytokines have failed. Thus, this study aimed to investigate the interplay between genetically predicted circulating concentrations of cytokines and the outcomes of sepsis and to identify potential targets for sepsis treatment.MethodsData related to 35 circulating cytokines in 31,112 individuals (including 11,643 patients with sepsis) were included in genome-wide association studies (GWASs) from the UK Biobank and FinnGen consortia. A bidirectional two-sample Mendelian randomization (MR) analysis was performed using single nucleotide polymorphisms (SNPs) to evaluate the causal effects of circulating cytokines on sepsis outcomes and other cytokines.ResultsA total of 35 inflammatory cytokine genes were identified in the GWASs, and 11 cytokines, including Interleukin-1 receptor antagonist (IL-1ra), macrophage inflammatory protein 1 (MIP1α), IL-16, et al., were associated with sepsis outcome pairs according to the selection criteria of the cis-pQTL instrument. Multiple MR methods verified that genetically predicted high circulating levels of IL-1ra or MIP1α were negatively correlated with genetic susceptibility to risk of sepsis, including sepsis (28-day mortality), septicaemia, streptococcal and pneumonia-derived septicaemia (P ≤ 0.01). Furthermore, genetic susceptibility of sepsis outcomes except sepsis (28-day mortality) markedly associated with the circulating levels of five cytokines, including active plasminogen activator inhibitor (PAI), interleukin 7 (IL-7), tumour necrosis factor alpha (TNF-α), beta nerve growth factor (NGF-β), hepatic growth factor (HGF) (P < 0.05). Finally, we observed that the causal interaction network between MIP1α or IL-1ra and other cytokines (P < 0.05).ConclusionsThis comprehensive MR analysis provides insights into the potential causal mechanisms that link key cytokines, particularly MIP1α, with risk of sepsis, and the findings suggest that targeting MIP1α may be a potential strategy for preventing sepsis.