IL-1ra Levels Research Articles

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.

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 characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity. Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two 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, gender, ethnicity, smoking status, and antiretroviral therapy (ART). Ninety-nine ART-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 LBP. 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 (aOR 2.7, 95% CI [1.7, 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]), 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 towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

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.

Blood cytokines as potential predictors of the development of SARS-CoV-2 associated pneumonia in patients with stage II ESSENTIAL hypertension

The search for predictors of the severe course of COVID-19 was relevant both during the pandemic and at the present time. The aim of the study was to analyze the relationship of cytokine levels in patients with EН before SARS-CoV-2 infection with the incidence of coronavirus pneumonia. Materials and methods. From the database of 290 patients with stage II EAG who have been under observation for 8–12 years with annual blood sampling to determine cytokine levels, COVID-19 survivors were selected (mild without pneumonia and moderate to severe, pneumonia CT 1–2, CT-3). Anamnestic levels of IL-1β, IL-1α, IL-1ra, IL-18, IL-18 BP, IL-37, IL-6, sIL-6r, M-CSF, VEGF-A, IL-34 and HMGB1) in the blood serum of patients with stage II EH were analyzed (method ELISA). The analysis of the obtained results was carried out using Stat Soft Statistica 13.5. Results and discussion. Patients with EH and COVID-19 with pneumonia (CT I-II) after SARS-CoV-2 infection 2–6 months before the infectious disease had significantly higher serum levels: IL-1α (p 0.05) and a decrease in IL-37 (p 0.001). During multivariate correlation analysis, a statistically independent relationship between an increase in the incidence of viral pneumonia in patients with stage II EН was confirmed only for IL-37 with a blood level of less than 60.2 pg/ml (regression coefficient — 2.21, standard error — 0.28, t criterion — 6.12, relative risk — 2.52, criterion Walda — 7.92, p = 0.006). When studying circadian rhythms of cytokine content in blood serum in patients of the analyzed groups, calculating the strength of correlations of anamnestic evening IL-37 levels in patients with stage II EР at 19.00–20.00 with the frequency of pneumonia against the background of SARS-CoV-2 infection, it has greater specificity and sensitivity (specificity — 0.75, sensitivity — 0.82) than morning concentrations. Considering that data on circadian rhythms were obtained in a limited number of patients, further monitoring is necessary, which is carried out by our scientific group. It should be noted that patients with essential hypertension are pathogenetically heterogeneous, including in terms of cytokine regulation. The study of this area will make it possible to personalize cytokine phenotypes of the disease and develop new methods for calculating the prognosis of both cardiovascular complications and features of the course of infectious diseases.

Plasma Immune Biomarkers Predictive of Progression to Active Tuberculosis in Household Contacts of TB Patients.

The progression from Mycobacterium tuberculosis infection to active tuberculosis (TB) disease varies among individuals, and identifying biomarkers to predict progression is crucial for guiding interventions. In this study, we aimed to determine plasma immune biomarker profiles in healthy household contacts of index pulmonary TB (PTB) patients who either progressed to TB or remained as non-progressors. A cohort of household contacts of adults with PTB was enrolled, consisting of 15 contacts who progressed to TB disease and 15 non-progressors. Plasma samples were collected at baseline, 4 months, and 12 months to identify predictive TB progression markers. Our findings revealed that individuals in the progressor group exhibited significantly decreased levels of IFNγ, IL-2, TNFα, IL1α, IL1β, IL-17A, and IL-1Ra at baseline, months 4 and 12. In contrast, the progressor group displayed significantly elevated levels of IFNα, IFNβ, IL-6, IL-12, GM-CSF, IL-10, IL-33, CCL2, CCL11, CXCL8, CXCL10, CX3CL1, VEGF, Granzyme-B and PDL-1 compared to the non-progressor group at baseline, months 4 and 12. ROC analysis identified IFNγ, GM-CSF, IL-1Ra, CCL2 and CXCL10 as the most promising predictive markers, with an AUC of ≥90. Furthermore, combinatorial analysis demonstrated that GM-CSF, CXCL10 and IL-1Ra, when used in combination, exhibited high accuracy in predicting progression to active TB disease. Our study suggests that a specific set of plasma biomarkers GM-CSF, CXCL10 and IL-1Ra, can effectively identify household contacts at significant risk of developing TB disease. These findings have important implications for early intervention and preventive strategies in TB-endemic regions.

Can Vitamin D Reduce Inflammation? The Influence of Supplementation on Selected Immunological Markers.

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing-remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance.

Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3β, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19.

Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

Cytokine Profiling in Cerebrospinal Fluid of Patients with Newly Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS): Associations between Inflammatory Biomarkers and Disease Activity.

Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies.

Physical Activity at Different Life Stages and Its Consequence on the Initial Immunization and Inflammatory Response Against COVID-19.

To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. Fifty-nine men and 56 women were evaluated before the first vaccine, and 12weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (β = 2012.077, 95% confidence interval, 257.7953-3766.358, P = .025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P = .025) and those that accumulated ≥150minutes per week of current moderate-vigorous PA (MVPA), and presented higher antibody production in relation to who did <150minutes per week of MVPA (P = .046). Individuals that were practitioners during childhood produced higher G-CSF (P = .047), and those that accumulated ≥150minutes per week of current MVPA demonstrated lower IP-10 levels (P = .033). However, PA practitioners during adolescence presented higher G-CSF (P = .025), IL-17 (P = .038), IL-1RA (P = .005), IL-1β (P = .020), and IL-2 (P = .026) levels. Our results suggest that adults that accumulated at least 150minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination.

Clinical characteristics, immunological alteration and distinction of MOG-IgG-associated disorders and GFAP-IgG-associated disorders

The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure.

The immune landscape of uterine fibroids as determined by mass cytometry

ObjectiveTo study the differences in immune cell profile in uterine fibroids (Fib) and matched myometrium (Myo). DesignObservational Study SettingLaboratory Study PatientsThe study included tissue that was collected from ten pairs of fibroid and matched myometrium from women, not on hormonal medications, undergoing hysterectomy and myomectomy. InterventionsNone Main Outcome MeasuresDifferences in immune cell and cytokine composition between fibroid and matched myometrium Result(s)The mass cytometry analysis indicated that fibroids had a significantly higher number of NK cells, total macrophages, M2 macrophages, and conventional dendritic cells when compared to matched myometrium from the same patient. In contrast, fibroids had significantly fewer CD3 and CD4 T cells when compared to myometrium. The mass cytometry analysis did not show any significant difference in the number of resting mast cells. IFC and IHC imaging confirmed the CytoF results, showing a significantly higher (p<0.05) number of NK, tryptase-positive mast cells indicative of mast cell activation, total macrophage, and M2 cells in Fibroids and a significantly lower (p<0.05) number of CD3 and CD4 T cells. The cytokine assay revealed significantly increased (p<0.05) levels of IFNA2, Il-1α, and PDGF-AA and significantly lower levels of M-CSF and IL-1RA in Fib. ConclusionOur results show significant differences in immune cell populations and cytokine levels between Fib and Myo. There was a significant increase in total number of macrophages, M2 macrophages, NK cells, and dendritic cells and a significant decrease in CD3 and CD4 T cells in Fib. IHC confirmed no differences in total resting mast cell count, but a significant increase in tryptase-positive mast cells in Fib. Fibs also expressed significantly higher levels of IFNA2, IL-1α, and PDGF-AA and significantly lower levels of IL-1RA and M-CSF as compared with matched myometrium. These findings provide a foundation for further studies exploring the role of immune cells in Fib development.

Innate immune responses are increased in children with acute asthma exacerbation.

Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation. We evaluated pro-inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation. Viral PCR was performed to differentiate between viral or non-viral-associated exacerbations. Following informed consent, clinical data were obtained from 20 children with asthma (median [interquartile range, IQR]: age 11.5 [8.0, 14.2]) years and 14 healthy age-matched controls (10.5 [7.0, 13.0]). Twelve had positive nasopharyngeal Polymerase chain reaction (PCR) for viral infection (11 rhinoviruses and 1 respiratory syncytial virus (RSV)). Nine were in the pediatric intensive care unit (PICU) and among them five required continuous positive airway pressure (CPAP). Mean (±SD) days on systemic steroids before drawing blood sample were 2.5 ± 1.6. Twelve had history of environmental allergies with 917 (274, 1396) IU/mL total IgE (median (IQR)). Compared with controls, IL-1RA and IL-10 levels were significantly increased and TNF-α significantly decreased in asthma subjects (p < .05 for all). RNA-seq analysis revealed 852 differentially expressed genes in subjects with asthma. Pathway analysis found upregulated genes and pathways involved in innate immune responses in subjects with asthma. Significantly reduced genes included pathways associated with T helper cell differentiation and activation. In acute asthma exacerbation, innate immune pathways remained increased while adaptive immune responses related to T helper cells are blunted and are independent of trigger or asthma severity. Our novel findings highlight the need to identify new therapies to target persistent innate immune responses to improve outcomes in acute asthma.

IL-1ra gene therapy in equine osteoarthritis improves physiological, anatomical, and biological outcomes of joint degeneration.

To evaluate the effects of a gene transfer approach to IL-1β inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. 16 horses were utilized for the study. All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra or saline in the osteoarthritis joint. Horses were evaluated over 70 days clinically (lameness, imaging, and biomarker analysis) and euthanized at 70 days and evaluated grossly, with imaging and histopathology. The following findings were statistically significant. Injection of scAAVIL-1ra resulted in high synovial fluid levels of IL-1ra (0.5 to 9 μg/mL) throughout the duration of the experiment (70 days). Over the duration, we observed scAAVIL-1ra to improve lameness (lameness score relative improvement of 1.2 on a scale of 0 to 5), cause suppression of prostaglandin E2 (a relative decline of 30 pg/mL), and result in histological improvement in articular cartilage (decreased chondrocyte loss and chondrone formation) and subchondral bone (less osteochondral splitting and osteochondral lesions). Within the synovial membrane of scAAVIL-1ra-treated joints, we also observed perivascular infiltration with CD3-positive WBCs, suggesting lymphocytic T-cell perivascular infiltration commonly observed with viral transduction. These data provide support for further evaluation and optimization of scAAVIL-1ra gene therapy to treat equine osteoarthritis.

Research Letter: Relationship of Blood Biomarkers of Inflammation With Acute Concussion Symptoms and Recovery in the CARE Consortium.

Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion. Multicenter study in National Collegiate Athletic Association member institutions including military service academies. Four hundred twenty-two participants with acute concussion. Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12hours, 12-36hours, and 36-60hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12hours; exploratory analyses were conducted with false discovery rate correction. For prespecified analyses, IL-1RA at 0 to 12hours in female participants was positively associated with more errors on the SAC (B(standard error, SE)=0.58(0.27), P <.05) and worse SCAT symptom severity (B(SE)=0.96(0.44), P <.05). For exploratory analyses, higher levels of IL-1RA at 12 to 36hours were associated with higher global (B(SE)=0.55(0.14), q<0.01), depression (B(SE)=0.45(0.10), q <0.005), and somatization scores on the BSI (B(SE)=0.46(0.12), q <0.01) in participants with concussion; Higher TNF at 12 to 36hours was associated with fewer errors on the SAC (B(SE)=-0.46(0.14), q <0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12hours was associated with slower RTP in female participants (OR=14.47; 95% confidence interval, 2.96-70.66, q <0.05); no other associations with recovery were observed. Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.

The regulation and potential role of interleukin-32 in tuberculous pleural effusion.

The possible protective effect of interleukin-32 (IL-32) in Mycobacterium tuberculosis (Mtb) infection has been indicated. However, few studies have been focused on IL-32 in tuberculosis patients. Additionally, the regulation of IL-32 production has rarely been reported. In the present study, the production, regulation, and role of IL-32 in tuberculous pleurisy (TBP) were investigated. We found that the content of IL-32 in tuberculous pleural effusion (TPE) was higher than the level in the malignant pleural effusion and transudative pleural effusion. The level of IL-32 mRNA in pleural fluid mononuclear cells (PFMCs) was higher than that in peripheral blood mononuclear cells (PBMCs) of patients with TBP, and this difference was mainly reflected in the splice variants of IL-32α, IL-32β, and IL-32γ. Compared with the PBMCs, PFMCs featured higher IL-32β/IL-32γ and IL-32α/IL-32γ ratios. In addition, lipopolysaccharide (LPS), Bacillus Calmette-Guérin (BCG), and H37Ra stimulation could induce IL-32 production in the PFMCs. IL-32 production was positively correlated with the TNF-α, IFN-γ, and IL-1Ra levels in TPE, whereas IFN-γ, but not TNF-α or IL-1Ra, could induce the production of IL-32 in PFMCs. Furthermore, IL-32γ could induce the TNF-α production in PFMCs. Monocytes and macrophages were the main sources of IL-32 in PFMCs. Nevertheless, direct cell-cell contact between lymphocytes and monocytes/macrophages plays an important role in enhancing IL-32 production by monocyte/macrophage cells. Finally, compared with the non-tuberculous pleural effusion, the purified CD4+ and CD8+ T cells in TPE expressed higher levels of intracellular IL-32. Our results suggested that, as a potential biomarker, IL-32 may play an essential role in the protection against Mtb infection in patients with TBP. However, further studies need to be carried out to clarify the functions and mechanisms of the IFN-γ/IL-32/TNF-α axis in patients with TBP.