IL-8 Levels Research Articles

Assessing the inflammation in pediatric MOGAD: Significance of CSF HMGB1 and related biomarkers

Background and purposeMyelin-oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a common inflammatory disease of the central nervous system (CNS) in children that can lead to demyelination. Evaluation and monitoring of biomarkers associated with its pathogenesis would provide vital information on disease progression and therapeutic assessment.MethodsWe assessed NLRP3, HMGB1, IL-6, and IL-33 levels in the cerebrospinal fluid (CSF) of pediatric patients with MOGAD at different time points and their association with the risk of disease. We recruited 30 patients with MOGAD (20 in the acute phase and 10 in remission) and 10 control patients with noninflammatory demyelinating disease. The expanded disability status scale (EDSS) was used to assess disease severity.ResultsNLRP3, HMGB1, and IL-6 levels in the CSF were significantly higher in patients with MOGAD during the acute phase than in remission (P < 0.05, P < 0.05, P < 0.05) and the control group (P < 0.01, P < 0.0001, P < 0.01). HMGB1 levels were significantly correlated with NLRP3 levels (P < 0.01) during the acute phase. Moreover, we found notable correlation between HMGB1 levels and EDSS (P < 0.05) scores. IL-6 levels were significantly correlated with the total number of attacks (P < 0.05), but not with EDSS scores.ConclusionsThese findings suggest that NLRP3, HMGB1, and IL-6 in the CSF may be potential therapeutic targets and are at least partly involved in the pathogenesis of pediatric MOGAD. HMGB1 in the CSF may be a potential biomarker correlating with pediatric MOGAD severity. Further investigations are warranted to validate potential cytokine pathways between that NLRP3, HMGB1, and IL-6 of MOGAD.

Downstream Link of Vitamin D Pathway with Inflammation Irrespective of Plasma 25OHD3: Hints from Vitamin D-Binding Protein (DBP) and Receptor (VDR) Gene Polymorphisms

Background: Vitamin D insufficiency/deficiency is a highly prevalent condition worldwide. At the same time, chronic inflammation is a versatile pathophysiological feature and a common correlate of various disorders, including vitamin D deficiency. Methods: We investigated the possible association of inflammation with 25-hydroxyvitamin D3 (25OHD3) levels and its down-stream pathway by exploring vitamin D-binding protein (DBP) and vitamin D receptor (VDR) genes for single-nucleotide polymorphisms (SNPs), in healthy non-elderly Bahraini adults. Plasma levels of 25OHD3 were measured by chemiluminescence, and six SNPs, four in the GC gene (rs2282679AC, rs4588CA, rs7041GT, and rs2298849TC) and two in the VDR gene (rs731236TC and rs12721377AG) were genotyped by real-time PCR. The concentrations of five inflammatory biomarkers, IL6, IL8, procalcitonin (PCT), TREM1, and uPAR, were measured by ELISA. Results: The results showed no association between the 25OHD3 level and any of the inflammatory markers’ levels. However, three tested SNPs were significantly associated with the concentrations of tested biomarkers except for IL6. The TT mutant genotype of rs2298849TC was associated with lower levels of IL8 and higher levels of PCT and TREM1, the AA mutant genotype of rs2282679AC was associated with decreased levels of IL8 (p ≤ 0.001) and increased levels of TREM1 (p = 0.005), and the GG wild genotype of rs12721377AG was associated with increased levels of 25OHD3 (p = 0.026). Conclusions: Although chronic inflammation is not associated with the vitamin D system in the blood, it is downstream, as revealed by DBP and VDR genotyping. Alternatively, DBP and VDR pursue other functions beyond the vitamin D pathway.

Immune imbalance in the pre-ovulatory follicular microenvironment of overweight and obese women during IVF

BackgroundOverweight and obesity can induce an inflammatory milieu in the oocyte microenvironment and are closely associated with reduced assisted reproductive outcomes.ObjectiveHow are immune cells, cytokines and lipid profiles altered in the pre-ovulatory microenvironment of overweight and obese women?Methods32 women undergoing in vitro fertilization (IVF) were included, with 14 overweight or obese (OW) and 18 normal weight (NW) participants. Serum was collected before ovulation induction, follicular fluid (FF) and aspirates were obtained during oocyte retrieval for flow cytometry, cytokines, hormone, and lipid profiles measurement. Clinical outcomes were recorded through a one-year follow-up.ResultsThe percentage of T cells in the pre-ovulatory follicular microenvironment, especially CD4+ T cells, increased significantly in the OW group, which positively related with BMI. Notably, type 2 cytokine IL4 and IL13 transcription level in OW group had significantly increased, while the type 1 cytokine IFNG only showed a non-statistically significant upward trend. Lipid profiles were screened, revealing no difference between the two groups, however, levels were higher in serum compared to FF. Additionally, the concentration gradient of TG between serum and FF was 22-fold in OW group (2.92 ± 3.66 vs. 0.13 ± 0.03), which was significantly higher than the 12-fold gradient observed in NW group (1.72 ± 0.95 vs. 0.14 ± 0.08). Furthermore, day 3 high quality embryos rate is negatively associated with BMI and exhibits a decreasing trend in OW group.ConclusionOverweight and obesity can disrupt immune hemostasis in the pre-ovulatory follicular microenvironment, potentially leading to adverse effects on assisted reproductive outcomes.

Urinary interleukin 13 level in steroid sensitive and resistant nephrotic syndrome: a cross-sectional single center study

Nephrotic syndrome, the most common glomerular disease in pediatric population, is classified into two groups of steroid sensitive (SSNS) and resistant (SSRS). There is growing evidence on the role of T cells cytokines, including interleukin-13, in pathophysiology of nephrotic syndrome and steroid response. This study was a cross-sectional study conducted at Children’s Medical Center Hospital in order to explore the relationship between urinary IL-13 levels and responsiveness to corticosteroid treatment. All children (1 to 15 years) referred from January 2021 to January 2022 diagnosed with nephrotic syndrome were included. Urine samples were collected during the initial phase or relapse of nephrotic syndrome, before the initiation of steroid or alternative treatments. Interleukin-13 levels in the urine were measured using the ELISA method. In this study, 83 cases of nephrotic syndrome were enrolled, of whom 30 (36.1%) were girls and 53 (63.9%) were boys. Out of the 83 cases, 63 (75.9%) were identified as SSNS and 20 (24.1%) as SRNS. There was no significant difference between the urinary interleukin-13 levels between SSNS and SRNS groups (P-value: 0.84). Sex (P-value: 0.598) and age (P-value: 0.704) also had no association with interleukin-13 levels. Further studies in larger population are recommended to better assess the potential of this biomarker to predict response to treatment. .

CCR2 signaling regulates anti-chlamydia T cell immune responses in the airway.

CCR2, a member of the G protein-coupled receptor (GPCR) superfamily, is widely expressed on monocytes, macrophages, activated T cells, and other cell types, and plays a critical role in coordinating the immune response to various infections. Here we demonstrate that CCR2 expression is significantly elevated during Chlamydia muridarum (C. muridarum) respiratory infection, and its absence leads to exacerbated susceptibility, as evidenced by significant weight loss, higher bacterial loads, severe lung pathology, and elevated levels of inflammatory cytokines (il-1β, tnfα, and il-6). The absence of ccr2 impairs both myeloid cell infiltration and T cell responses, which are crucial for effective immune defense. Specifically, ccr2 deficiency disrupts the differentiation and response of Th1 cells, which are the primary effector lineage responsible for clearing chlamydia through secretion of interferon-gamma (IFN-γ). As a result, there is a significant decrease in CD3+CD4+IFN-γ+ T cells in the lung and spleen, accompanied by reduced levels of IFN-γ protein and mRNA, as well as downregulated mRNA expression of Th1-promoting cytokines (il-12p35, il-12p40) and transcription factors (stat4, T-bet), which play crucial roles in Th1 differentiation. Moreover, ccr2 deficiency greatly diminishes STAT1 phosphorylation, a key regulator of IFN-γ secretion by Th1 cells. Meanwhile, we also observed a significant reduction in IFN-γ secretion by CD8+ T cells following ccr2 deficiency. Conversely, ccr2-/- mice exhibit an exaggerated Th2-type immune response, with elevated levels of Th2-promoting cytokines (IL-4), transcription factors (STAT6 and gata3), and il-5, which together lead to more severe lung tissue damage and increased susceptibility to infection. Furthermore, these mice show higher levels of IL-17 along with an enhanced Th17-type immune response, characterized by increased Th17-promoting cytokines TGFB, transcription factors stat3 and RORγt, and il-21, suggesting a compensatory mechanism that drives neutrophil infiltration to exacerbate lung inflammation. These findings underscore the pivotal role of CCR2, a chemokine receptor, in orchestrating the immune response to Chlamydia infection by facilitating Th1 cells differentiation while restraining Th2-type and Th17-type immune responses, thereby alleviating pulmonary inflammation.

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.

Concurrent exercise training during pregnancy is related to more favourable maternal lipid levels when IL-8 increases

ABSTRACT It is unclear how exercise-induced stimuli affect and translate into immunometabolic adaptations during pregnancy. We previously found that exercise influences maternal-foetal circulating cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α). This study investigated i) the influence of an exercise training programme during pregnancy on metabolic markers (glycaemic and lipid markers, and C-reactive protein) in maternal, and cord arterial and venous serum; and ii) whether these cytokines mediated the effects of exercise on metabolic markers. Eighty-eight pregnant women, divided into exercise (n = 44) and control (n = 44) groups, participated in this quasi-experimental study. The exercise group followed a 60-min 3 days/week concurrent (aerobic+resistance) exercise training. Glycaemic and lipid markers and C-reactive protein concentrations, and cytokines levels, were measured at weeks 17 and 34 and birth with standard biochemical methods and Luminex xMAP technology. Overall, exercise did not induce detectable changes in maternal metabolic markers during pregnancy, except for those exercisers whose IL-8 levels increased, where it was related to lower maternal total cholesterol (indirect effect= −9.1; 95% CI= −24.6, −1.1) and low-density lipoprotein-cholesterol gains (−8.9; −21.9, −1.1). This suggests a mechanism by which exercise may optimise lipid metabolism regulation. Moreover, exercise was related to lower cord arterial serum glucose levels. Further research, especially concerning foetal metabolism, is necessary.

Food Intolerance and Allergy: Do They Have an Etiological Role in Idiopathic Granulomatous Mastitis?

Background/Objectives: Despite its long-standing recognition, the etiopathogenesis of idiopathic granulomatous mastitis (IGM) remains poorly understood. This study aims to investigate the relationship between IGM and food intolerance, allergies, and immunological factors to shed light on its etiology. Materials and Methods: This case–control study included 32 patients with IGM and 32 healthy women. In order to examine their potential relevance to allergy and immunology, serum interleukin (IL)-4, IL-4 receptor, histamine, and histamine-releasing factor (HRF) were measured by ELISA. Furthermore, serum IgG antibodies against specific food allergens were measured to evaluate food intolerance. Results: The patient group exhibited significantly higher intolerance values for lentils and curry compared to the control group (p = 0.023 and p = 0.012, respectively). Histamine (p < 0.001) and IL-4 (p = 0.003) levels were elevated in IGM patients compared to the control group, while HRF and IL-4R outcomes did not show any significant differences (p > 0.05). Conclusions: Elevated histamine and IL-4 levels may suggest the involvement of allergy and immunological factors in IGM’s etiopathogenesis. The integration of anti-histamine medications for IGM patients with elevated histamine levels could provide an alternative therapeutic strategy.

Augmented IFNγ producing ILC1 and IL 17 producing ILC3 in pemphigus vulgaris: Plausible therapeutic target.

Innate Lymphoid cells (ILCs) are innate counterparts of helper T cells. Although low in number, they have proven to play major roles in many autoimmune diseases. In Pemphigus Vulgaris (PV), the gaps in the knowledge of functional role of ILCs remain. To bridge the gap, our study investigated the phenotype along with the functional determinants of ILCs involved in PV immunopathogenesis. Our data suggested augmentation in overall ILC population in circulation of PV patients. Specifically, ILC1 and ILC3 subtypes were significantly increased in peripheral circulation of PV patients compared to healthy controls. We observed no changes in ILC2 population. mRNAs from ILC enriched population showed significant upregulation in transcription factors- ID2, T bet and RORγt and a downregulation in GATA3 and RORα. The mRNA levels of ILC related cytokines- IFNγ and IL17 were significantly upregulated while no change was observed in the levels of IL13, IL 22, AHR. The levels of autoantibodies against desmoglein (Dsg) 3 which is the characteristic of PV pathogenesis were also checked in the serum which confirmed significant upregulation in PV patients. The levels of proinflammatory- IFNγ, IL 17 and IL 15 were elevated and anti-inflammatory cytokines- IL10 was downregulated in the serum of PV patients. The results of this study offer insights into the functional attributes of ILCs and related cytokines, potentially contributing to the development of future therapeutic interventions.

A multicenter, prospective phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to anti-EGFR agents (HGCSG1801): Updated analyses.

147 Background: The HGCSG1801 trial evaluated the treatment outcomes of aflibercept (AFL) plus FOLFIRI for patients(pts) with metastatic colorectal cancer (mCRC) refractory to an oxaliplatin-based regimen combined with an anti-EGFR agent. Here we report results of the updated efficacy, safety, and a biomarker analysis. Methods: This was a prospective open-label phase II trial. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m 2 , leucovorin 200 mg/m 2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m 2 , and infusional 5-FU 2400 mg/m 2 /46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was 6-month progression-free survival (PFS) rate, and the secondary endpoints included overall survival (OS), PFS, overall response rate (ORR), disease control rate (DCR), and adverse events. Angiogenic factors were analyzed in plasma sample using a Luminex multiplex assay using the Cox proportional hazards model. This study was sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and supported by a grant from Sanofi. Results: Forty-three pts were enrolled between November 2019 and October 2022. The data cut-off date was April 30, 2024. The 6-month PFS rate was 59.0% (90% confidence interval [CI], 45.8–72.1%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The ORR was 20.9% (95% CI, 10.0–36.0%) and DCR was 88.4% (95% CI, 74.9–96.1%). No deaths and no new safety signals with a causal relation to the study treatment were observed. A biomarker analysis using pretreatment plasma samples showed a trend toward better PFS in pts with low VEGF-A (hazard ratio [HR] 0.40 [95% CI, 0.18-0.91]), TSP-2 (HR 0.40 [95% CI, 0.18-0.88]) or IL-8 levels (HR 0.43 [95% CI, 0.20-0.93]). There was also a trend toward better OS in pts with low levels of TSP-2 (HR 0.30 [95% CI, 0.11-0.81]) or TIMP-1 (HR 0.20 [95% CI, 0.06-0.69]). Conclusions: These updated data further support the activity and manageable safety profile of AFL plus FOLFIRI for pts with mCRC who failed an oxaliplatin-based regimen combined with an anti-EGFR agent. It was suggested the association between some angiogenic factors in plasma samples and the activity of AFL plus FOLFIRI in mCRC. Clinical trial information: jRCTs011190006 .

Childhood allergy and anxiety/depression in early adulthood: A longitudinal study in the ALSPAC birth cohort.

Allergic disease and common mental disorders frequently co-occur. However, little is known about the longitudinal impact of childhood allergy on the subsequent risk of developing anxiety or depression, and the possible biological mechanisms for this. We performed longitudinal analyses of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. The baseline sample comprised n=5256 children with allergy data available at age 7yrs. We used multivariable regression to test associations between childhood allergy at age 7yrs and: a) four inflammatory markers at age 9yrs; b) depression and anxiety measures between ages 10-24yrs. Allergy measures included biological markers (total serum immunoglobulin E (tIgE), number of positive skin prick tests (SPTs)), and presence of eczema, asthma and/or food allergy (mother reported). Inflammatory markers were interleukin-6 (IL-6), C-reactive protein (CRP), IL-4 and IL-13. We used structural equation modelling to test whether inflammatory markers mediated the association between tIgE and depression/anxiety. tIgE and having≥1 positive SPT at age 7 were associated with IL-6 levels at age 9 (adjusted β=0.09; 95% CI 0.06-0.13; p<0.001 and adjusted β=0.06; 95% CI 0.03-0.09; p<0.001 respectively), but not with CRP, IL-4 or IL13 levels. We found no strong evidence of an association between childhood allergy and subsequent depression/anxiety during adolescence and early adulthood. This finding was consistent across biological and mother-reported allergy measures. Biological markers of childhood allergy are associated with IL-6, a key inflammatory cytokine. However, childhood allergy may not have a large long-term effect on subsequent depression/anxiety.

Impact of microbial diversity on inflammatory cytokines and respiratory pattern measured in whole-body plethysmography in guinea pig models.

This study investigates the breathing patterns and immune status of guinea pigs raised under specific pathogen-free (SPF) conditions compared to conventionally bred (CON). Breathing pattern parameters were assessed using whole-body plethysmography (WBP) during quiet breathing and saline nebulisation. Blood and bronchoalveolar lavage fluid (BALF) were analysed for white blood cell, neutrophil and eosinophil counts, and cytokine levels (TNF-α, IL-1β, IL-4). SPF guinea pigs exhibited higher tidal volume, expired volume, minute volume, and airflow parameters than CON guinea pigs. The immune analysis revealed lower white blood cell counts and IL-4 levels in SPF guinea pigs. These findings indicate that SPF guinea pigs have different respiratory and immune responses than CON guinea pigs. The study highlights that the maturation processes affecting breathing pattern parameters in SPF guinea pigs differ significantly from those in CON guinea pigs. This suggests potential limitations of SPF animals in respiratory physiology research due to their different immune and respiratory responses.

Inflammatory factors predict infection risk during chemotherapy in leukemia patients.

This study explores the novel role of specific inflammatory factors in predicting infection risk among leukemia patients undergoing chemotherapy, providing new insights into managing leukemia-associated infections. This prospective cohort study included 244 leukemia patients suspected of infection, divided into the infected group (n=194) and the uninfected group (n=50) based on etiological testing. The infected group was further categorized into bacterial (n=123), fungal (n=22), and viral (n=49) infection subgroups. Inflammatory cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, IFN-γ, IL-17A, IL-127P0, and IFN-α were measured using ELISA kits. Additional markers such as hs-CRP, SAA, and PCT were also assessed for the infected group. The levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, IL-12p70, and IFN-α significantly differed between the infected and uninfected groups (P<0.05). IL-1β, IL-4, IL-6, and IL-10 were significantly higher in the infected group compared to the uninfected group. Significant differences in PCT, IL-2, IL-4, IL-5, and IL-10 levels were observed among patients with bacterial, fungal, and viral infections (P<0.05). However, none of these inflammatory factors were predictive of infection type. IL-4, IL-6, IL-8, and IL-10 were identified as independent predictors of infection risk. However, no inflammatory factors could be used to distinguish between different types of infections.

Peripheral protein inflammatory biomarkers in bipolar disorder and major depressive disorder: A systematic review and meta-analysis.

Bipolar disorder (BD) and major depressive disorder (MDD) are mood disorders. The most frequent clinical presentation of BD and MDD is depression, which contributes to high rates of misdiagnosis between disorders. To support diagnostic discrimination and therapeutic stratification, we aim to perform a systematic review and meta-analysis evaluating peripheral protein inflammatory biomarkers between BD and MDD, with a focus on the depressive state. We conducted a literature search on PubMed, PsycInfo and Embase with no year/language restrictions. Original studies including human participants with a BD or MDD diagnosis which directly compared levels of peripheral protein inflammatory biomarkers between groups were included. A random effects meta-analysis was performed. 35 studies were included in the systematic review. 9 studies were included in the meta-analysis. The meta-analysis showed IL-7 (p < 0.01) levels were significantly decreased in BD, and IL-9 (p < 0.01), CCL3 (p = 0.03), CCL4 (p = 0.01), CCL5 (p = 0.02) and CCL11 (p = 0.04) levels were significantly increased in BD. High heterogeneity and limited dataset size restricted our meta-analysis to a small subset of biomarkers and limited our exploration of the effects of moderator variables. This study found differences in IL-7, IL-9, CCL3, CCL4, CCL5 and CCL11 between BD and MDD in a depressive state. These findings support the notion that inflammation is associated with mood disorder pathophysiology, particularly with respect to T-cell network dysregulation. Further studies can assist in better understanding differences between disorders and work towards clinical applications.

Human Parvovirus B19 infection in a Plasmodium vivax endemic area on the Brazil-French Guiana border.

While human parvovirus B19 (B19V) infection is widespread in Brazil, over 99% of reported malaria cases occur in the Amazon region, mainly by Plasmodium vivax. As B19V infection may contribute to anemia in children living in P. falciparum endemic areas, this study aimed to investigate the impact of B19V/P. vivax coinfection in residents of the municipality of Oiapoque, Amapá, Brazil. A total of 300 serum samples collected in 2014-2015, from individuals infected by P. vivax (n=148) and non-infected (n=152), were tested for B19V by serologic and molecular methods. Hemoglobin dosage and cytokine levels were evaluated by automatic method and flow cytometry/ELISA, respectively. Acute B19V infection was diagnosed in 56.8% (84/148) of infected with P. vivax and 38.2% (58/152) of non-infected individuals (p<0.01), and P. vivax was considered a risk factor for B19V infection (OR=2.19; 95% CI; p=0.001). Participants were grouped into: B19V/P. vivax coinfected (CO), P. vivax monoinfected (M), B19V monoinfected (B19V), and endemic control (EC) who were negative for both agents. A significant association was found between the CO group and lower hemoglobin levels (RRR= 0.66; 95% CI; p=0.0019), but no link was found between anemia and coinfection. It was found that higher gametocyte count (OR=1.002; 95% CI; p=0.0164), IL-5 (RRR=1.74, 95% CI; p=0.025) and IL-10 (RRR=1.45; 95% CI; p=0.004) levels were strongly associated with the CO group. No difference in viral load was observed between the CO and B19V groups. Our study highlights the importance of monitoring the circulation of B19V in P. vivax endemic areas.

Interleukin-13 partly induced by the NLRP3 inflammasome promotes Trichinella spiralis encapsulation in infected mice.

Trichinella spiralis infection is a serious parasitic zoonosis in which a collagenous capsule surrounding the larva is developed in the striated muscle cells. However, the mechanism of T. spiralis encapsulation is currently poorly understood. It has been reported that T. spiralis infection can induce the production of IL-13 via the NLRP3 inflammasome, and it has also been suggested IL-13 thus produced may be involved in T. spiralis encapsulation. This research aimed to clarify the involvement of NLRP3 and IL-13 in the T. spiralis capsule formation process. IL-13 and NLRP3 inhibitors were used in a T. spiralis infected mouse model and in C2C12 cells to analyze the role of IL-13 and NLRP3 in encapsulation. The results showed that T. spiralis infection significantly increased the expression levels of IL-13 and collagen IV and VI. The production of collagen around the T. spiralis encapsulation zone was significantly inhibited when an IL-13 inhibitor was applied. Moreover, the expression levels of IL-13 and collagen IV and VI were significantly decreased by the NLRP3 inhibitor in vitro and in vivo. The above results indicated that NLRP3 can participate in the development of T. spiralis encapsulation by regulating IL-13 expression and stimulating collagen IV and VI synthesis during T. spiralis infection.

Luteolin alleviates olfactory dysfunction in eosinophilic chronic rhinosinusitis through modulation of the TLR4/NF-κB signaling pathway.

Eosinophilic chronic rhinosinusitis (ECRS) is characterized by early, severe olfactory dysfunction and a high recurrence rate, with inadequate treatments. This article aims to elucidate the potential mechanisms by which luteolin may treat olfactory dysfunction in the context of ECRS. Thirty C57 BL/6 mice were randomly assigned to five groups: a control group and four experimental groups (ECRS, ECRS+Luteolin (Low, Medium, High Dose)). We conducted RNA sequencing, behavioral testing, ELISA, PCR, HE staining, Western blot analysis, and immunofluorescence staining. Additionally, human olfactory epithelial Cells (HOEPCs) were treated with Luteolin, TAK-242, QNZ, and Luteolin+LPS to investigate the underlying mechanisms. Luteolin significantly reduced IL-4, IL-5, and IL-13 levels in the nasal lavage fluid (NLF) of ECRS mice, improving olfactory function and restoring OMP+ mature and Gap43+ immature olfactory sensory neurons (OSNs). RNA sequencing revealed the involvement of the TLR4/NF-κB pathway in ECRS-related olfactory dysfunction and luteolin's therapeutic effects. Luteolin reduced TLR4+ cells, P65 nuclear translocation, and decreased protein levels of IL-1β, TLR4, MyD88, p-P65, P65, and p-P38. The treatment also lowered OSNs cell apoptosis by decreasing the levels of cleaved caspase-3 and caspase-9 levels, and increasing Bcl-2 protein. Antioxidant enzymes SOD, CAT, and GSH-Px were elevated, while MDA levels decreased. In ECRS HOEPCs, luteolin's anti-apoptotic effects on OSNs were reversed by LPS-induced TLR4/NF-κB activation. Luteolin ameliorates olfactory dysfunction associated with ECRS by modulating the TLR4/NF-κB signaling pathway. This modulation results in a reduction of TH2-type inflammation, oxidative stress, and apoptosis in OSNs.

Phenotypes of antigen-induced responses in guinea pigs: Beyond the asthma model.

Asthma is a heterogeneous and variable disease. In an allergic asthma model using guinea pigs (GPs), we identified three distinct phenotypes: those always showing an obstructive response (R), those never responding (NR), and those sometimes responding (VR). We aimed to assess and compare the functional and immunological characteristics of these groups. GPs were sensitized and challenged with ovalbumin (OVA) every 10 days in a plethysmographic chamber to measure the maximum obstructive response. The control group was sensitized and challenged with saline. Control and NR GPs never duplicated baseline obstruction values. At least three antigenic challenges were needed to identify each phenotype. None of the groups showed late responses. Analysis of at least six antigenic challenges in 125 GPs revealed that 48 % were R, 20 % NR, 29 % VR, and 8 % died from anaphylactic shock. R GPs did not develop antigenic tolerance. During the third or twelfth challenges, we evaluated antigen-induced airway reactivity to histamine: R GPs consistently showed hyperreactivity, NR showed hyperreactivity only on the third challenge, while VR and control groups never showed hyperreactivity. Serum levels of anti-OVA IgE and IgG1 were elevated in all groups compared to controls. IL-4 levels in the lungs and eosinophils counts in bronchoalveolar lavage fluid (BALF) of R and VR were higher than to controls and NR. The number of mast cells in the airway wall also increased in R and VR compared to controls. IFN-γ levels were similar across all groups on the third challenge but increased significantly in NR on the twelfth challenge compared to the other groups. Neutrophil counts in BALF increased in R and VR, and in NR but only at the twelfth challenge compared to controls. Our findings suggest that R and VR guinea pigs serve as valid models for asthma, with VR representing a distinct phenotype characterized by variability and lack of hyperreactivity. Conversely, NR guinea pigs, despite their high IgE and anti-OVA IgG1 levels and hyperresponsiveness at the third challenge, do not align with typical asthma characteristics.

Dynamics of tissue repair regulatory T cells and damage in acute Trypanosoma cruzi infection.

Tissue-repair regulatory T cells (trTregs) comprise a specialized cell subset essential for tissue homeostasis and repair. While well-studied in sterile injury models, their role in infection-induced tissue damage and antimicrobial immunity is less understood. We investigated trTreg dynamics during acute Trypanosoma cruzi infection, marked by extensive tissue damage and strong CD8+ immunity. Unlike sterile injury models, trTregs significantly declined in secondary lymphoid organs and non-lymphoid target tissues during infection, correlating with systemic and local tissue damage, and downregulation of function-associated genes in skeletal muscle. This decline was linked to decreased systemic IL-33 levels, a key trTreg growth factor, and promoted by the Th1 cytokine IFN-γ. Early recombinant IL-33 treatment increased trTregs, type 2 innate lymphoid cells, and parasite-specific CD8+ cells at specific time points after infection, leading to reduced tissue damage, lower parasite burden, and improved disease outcome. Our findings not only provide novel insights into trTregs during infection but also highlight the potential of optimizing immune balance by modulating trTreg responses to promote tissue repair while maintaining effective pathogen control during infection-induced injury.

High HIV-1 viremia and low anti-Env antibody responses are associated with delayed treatment response to fostemsavir in highly treatment-experienced individuals.

Fostemsavir (FTR) is an approved first-in-class small molecule Env antagonist for treating multi-drug resistant (MDR) HIV-1 infection. In the BRIGHTE study, viral suppression rates in heavily treatment-experienced people with HIV (PWH) increased from week 48 through week 96. Factors that contribute to this late response are not well understood. Given FTR's ability to stabilize a native HIV-1 envelope trimer conformational state, we examined anti-HIV humoral immune responses in the BRIGHTE study to explore how evolving antibody responses in the presence of drug correlate with delayed viral suppression. 16 BRIGHTE study participants (ppt) were selected based on their time to first viremic suppression: eight early (EVS) and eight late viral suppressors (LVS). Immune responses were also analyzed in eight ppt from the SAILING study that evaluated dolutegravir. Anti-HIV Env IgG titer, cell-free and cell-to-cell neutralization activity, FcγRIIa- and FcγRIIIa-signaling, and plasma cytokines at weeks 0, 4 and 108 were examined and correlated with clinical variables associated with treatment response. FTR treatment did not significantly enhance antibody responses against reference strain of HIV in LVS compared to EVS. However, at baseline, LVS had significantly lower anti-HIV IgG titers, higher VL, lower CD4+ T-cell counts and experienced greater increases in CD4+ T-cell counts than EVS. Additionally, IL-8 levels were increased in LVS vs. EVS at treatment initiation. In comparison, SAILING ppt showed increased FcγRIIa signaling during drug treatment compared to the FTR groups. Further studies will determine if pre-treatment characteristics influence timing to viral suppression in FTR-treated individuals with MDR-HIV.