Levels Of Th2 Cytokines Research Articles

Diagnostic utility of Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) in pulpal blood for assessing pulpitis severity

ObjectiveTo evaluate the diagnostic utility of T-helper type 2 (Th2) cytokines, specifically Interleukin-4 (IL-4), IL-5, IL-10, and IL-13, in distinguishing different stages of pulpitis and their combined performance in clinical diagnosis.MethodsA total of 161 participants were enrolled and categorized into normal pulp (NP, n = 45), reversible pulpitis (RP, n = 75), and symptomatic irreversible pulpitis (IP, n = 41). Th2 cytokine levels in pulpal blood samples were measured using enzyme-linked immunosorbent assays (ELISA).ResultsTh2 cytokine levels (IL-4, IL-5, IL-10, and IL-13) were significantly elevated in pulpitis cases compared to normal pulp, with the highest concentrations observed in symptomatic IP. Diagnostic analysis showed that IL-4 and IL-13 had the highest diagnostic accuracy for distinguishing pulpitis (both RP and IP) from normal pulp, with AUCs of 0.91, and perfect specificity (100%). IL-5 demonstrated the best balance between sensitivity (68%) and specificity (97%) for differentiating IP from NP (AUC = 0.84). IL-13, though less effective overall, provided moderate accuracy (AUC = 0.63) for distinguishing RP from NP. Additionally, the combined diagnostic model of all four cytokines achieved high AUCs, particularly in distinguishing irreversible pulpitis from normal pulp (AUC = 0.94) and irreversible pulpitis from reversible pulpitis (AUC = 0.90).ConclusionsTh2 cytokines, especially IL-4, IL-5, and IL-13, are effective biomarkers for identifying different stages of pulpitis. Their elevated levels, particularly in irreversible pulpitis, provide strong diagnostic accuracy. Combined cytokine analysis enhances diagnostic precision, making Th2 cytokine profiling a valuable tool for assessing pulpitis severity.

Cure for the itch: current clinical standards and therapies in allergic eczema.

Allergic Eczema (AE) is a chronic, relapsing skin condition that significantly affects the quality of life of the AE patients and their caretakers. Decades of scientific and clinical research has helped understand the highly complex underpinnings of AE presentation wherein a multitude of variables, including the conspicuous variables such as environmental allergens, immunological triggers, genetic predisposition of individuals, to more nuanced socio-economic status, play an important part. Given the complexity of the disease, it is imperative to develop biomarkers enabling early and reliable clinical identifications and help in the active management of the disease, thereby minimizing the impact and burden of the disease on the patients. In this mini review, we provide a brief overview of AE, affected demographics, variables that trigger its onset, and summarize the discovery of various clinical biomarkers such as total and specific serum IgE levels, Th2 cytokine levels, filaggrin (FLG) mutations, periostin levels in skin, etc. that have been developed over the years to further improve the state of clinical monitoring of AE presentation and progression. Lastly, we also provide an overview of the clinical interventions and therapies, such as topical agents, phototherapy, and biologics, that are available to the patients to manage AE-related complications. While we have vastly improved the standard of care and diagnosis for the AE patients, there are still many unmet needs such as developing non-invasive, effective, and reliable clinical predictors and biomarkers which can usher better personalized treatments and provide a better quality of life to affected demographics.

Eupatorin Mitigates Airway Inflammation in Ovalbumin-Induced Allergic Asthma in Mice by Regulating Th2 Cytokines and Oxidative Stress.

Asthma is a prevalent airway inflammatory condition caused by exposure to various allergens. It is defined by the presence of airway inflammation, airway hyperresponsiveness, and excessive production of mucus. This work was undertaken to study the curative potentials of eupatorin against ovalbumin (OVA)-exposed asthma in mice. The influence of eupatorin on the RAW 264.7 cell growth were assessed by MTT test. The inflammatory cytokines and nitric oxide (NO) concentration in the RAW 264.7 cells was examined using kits. The antibacterial effects of eupatorin against H. influenza, S. pneumoniae, and C. pneumoniae were evaluated using the well diffusion technique. The impact of eupatorin on the inflammatory cells in OVA-treated asthma mice was evaluated. The Th2 cytokines, TNF-α, IgE, and IFN-γ weres evaluated using assay kits. The oxidative stress parameter levels were examined using the kits. The histopathological examination was performed on the lungs of the experimental mice. The current work demonstrates that the eupatorin treatment did not affect the RAW 264.7 cell growth. It also reduced the NO, TNF-α, and IL-6 concentrations in the LPS-exposed RAW 264.7 cells. Furthermore, the eupatorin treatment to OVA-induced mice led to a diminution in Th2 cytokine levels and inflammatory cell counts. The eupatorin treatment was found to decrease OVA-specific IgE and pro-inflammatory markers, which results in the alleviation of airway inflammation. The eupatorin treatment also improved the antioxidant status. The findings of the histopathological analysis demonstrated the curative properties of eupatorin against on asthmatic mice. The anti-asthmatic effects of eupatorin are attributed to its capacity to decrease airway inflammation and enhance antioxidant processes. Therefore, it is evident that eupatorin possesses anti-asthmatic properties, making it a promising therapeutic candidate to treat allergic asthma.

Abstract A106: Synergistic Effects of CD40 Agonist Antibody and DC-Derived Exosomes Enhance Anti-Tumor Efficacy by Modulating the Tumor Microenvironment and Reducing Metastasis in a Murine Melanoma Model

Abstract Over the past decade, dendritic cell (DC) vaccines have been extensively studied to reprogram the tumor microenvironment (TME) and delay tumor growth. However, limitations related to long-term storage, patient- specific variability, short half-life, and moderate anti-tumor efficacy highlight the need for further refinement of DC vaccines for effective cancer treatment. As an alternative, DC-derived exosomes (DeX) have demonstrated superior anti-tumor efficacy and stability compared to DCs. However, within tumors, low expression of co- stimulatory molecules such as CD40, CD86, and CD80 limits the effectiveness of these cancer vaccines. The use of a CD40 agonist antibody (αCD40) has shown potential in increasing CD40 expression, enhancing antigen presentation, and contributing to a robust anti-tumor response. In this study, we demonstrate that combining αCD40 with DeX pulsed with cancer cell lysate significantly delayed tumor growth and improved survival in mice bearing B16-F10 melanoma. In tumor, the combination therapy increased the population of CD45+CD8+ T-cells and CD45+CD20+ B-cells, while reducing PD-L1 expression. Additionally, the combination therapy boosted levels of Th1 cytokines (IFN-γ, IL-6, IL-2) compared to Th2 cytokines (IL-4 and IL-10), supporting an enhanced anti-tumor response. Importantly, this approach also augmented anti-tumor immunity in the spleen, significantly lowered the expression of metastatic markers including vimentin, and fibronectin in the primary tumor, and reduced lung metastasis. Overall, these findings suggest that the combined use of αCD40 and DeX is a promising strategy to improve the in vivo anti-tumor efficacy of DC vaccines and supports further exploration of this novel combinatorial therapy in clinical settings. Citation Format: Vidit Gaur, Jayanta Bhattacharyya. Synergistic Effects of CD40 Agonist Antibody and DC-Derived Exosomes Enhance Anti-Tumor Efficacy by Modulating the Tumor Microenvironment and Reducing Metastasis in a Murine Melanoma Model [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A106.

Investigation of the Relationship Between IL-17, IL-27, IL-2 Blood Levels in Spontaneous Abortion and Healthy Pregnant Women.

Cytokines are essential for regulating immune cell activity during pregnancy. Research shows that CD4+ T-cells exhibit specific cytokine secretion patterns, resulting in polarized immune responses. This study aims to compare the gene expression levels of Th1, Th2, and Th17 cytokines in women with normal pregnancies versus those with a history of recurrent spontaneous abortion (RSA). In this case-control study, 20 patients with RSA within 24 h of their last abortion were compared to 20 pregnant women with no history of abortion (Control Group). Cytokine levels of IL-2, IL-17, and IL-27 were quantified using real-time polymerase chain reaction (RT-PCR). Overall cytokine levels were similar between the groups, but the cytokine levels in both groups were generally similar. However, higher IL-17 and IL-2 levels were observed in the healthy pregnancy group (p = 0.006 and p = 0.001, respectively). Elevated IL-17 and IL-27 levels were observed in healthy pregnancies, whereas lower levels were seen shortly after a miscarriage. IL-27 levels were significantly higher in women with recurrent abortions compared to those with healthy pregnancies (p < 0.001). Elevated IL-2 levels may be a risk factor for RSA. Consistent with recent studies, our findings emphasize the role of IL-17 and IL-27 as crucial regulatory cytokines for maintaining a successful pregnancy.

Antagonism of CD28 blocks allergic responses in the ovalbumin-induced asthmatic model mice.

Antagonism of CD28 blocks allergic responses in the ovalbumin-induced asthmatic model mice.

A VZV-gE subunit vaccine decorated with mPLA elicits protective cellular immmune responses against varicella-zoster virus.

A VZV-gE subunit vaccine decorated with mPLA elicits protective cellular immmune responses against varicella-zoster virus.

Inhibition of DNA Methyltransferase DNMT1 Reverses Th2 Response Polarisation and Alleviates Allergic Rhinitis.

Type 2 T helper (Th2) cells-mediated immune response plays vital roles in allergic rhinitis (AR), and DNA methylation is previously found to be closely related to AR development. Our study aims to reveal the detail mechanism of DNA methylation affecting Th2 response in AR. Mice were stimulated with ovalbumin (OVA) to induce AR symptoms, and CD4+ T cells were subjected to Th2 induction culture. Real-time quantitative PCR, western blot, flow cytometry, and enzyme-linked immunosorbent assay were performed to analyse the activation of Th2 response. DNA methyltransferase 1 (DNMT1) was significantly upregulated in OVA-induced AR model mice, and DNMT1 knockdown alleviated AR symptoms and pathological changes of nasal mucosa tissues in the model mice. DNMT1 knockdown obviously reduced the expression of GATA binding protein 3 (GATA3), the ratio of interleukin (IL)-4+CD4+ cells and the release of Th2 cytokines, but elevated the expression of T-box expressed in T cells (T-bet), the ratio of interferon (IFN)-γ+CD4+ cells and the levels of Th1 cytokines to improve Th1/Th2 imbalance in the model mice and Th2-induced CD4+T cells. Mechanistically, DNMT1 promoted promoter methylation of forkhead box O3 (FOXO3), inhibited FOXO3 expression and activated the nuclear factor kappa-B (NF-κB)/GATA3 signalling. FOXO3 overexpression remarkably inactivated the NF-κB/GATA3 pathway and mitigated Th2 polarisation in DNMT1-deficient and Th2-conditined CD4+T cells, which was reversed by a NF-κB inhibitor. Altogether, DNMT1 downregulated FOXO3 expression to activate the NF-κB/GATA3 pathway and promote Th2 response in AR.

Development and immunogenicity evaluation of attenuated Salmonella typhimurium delivering porcine Deltacoronavirus S1 gene.

Development and immunogenicity evaluation of attenuated Salmonella typhimurium delivering porcine Deltacoronavirus S1 gene.

Protein regulator of cytokinesis 1 regulates autophagy in hepatitis B virus‑associated liver cancer development.

Protein regulator of cytokinesis 1 regulates autophagy in hepatitis B virus‑associated liver cancer development.

P1190 Generation of blood-derived reference samples with endogenous cytokines

Abstract Background Biomarkers have become an integral part of drug development and decision-making. The quantification of cytokines, commonly used to gain insights into pathological processes in indications such as Inflammatory Bowel Diseases (IBD), and for monitoring therapeutic intervention, should rely on robust and performant methods. Relevant reference samples are crucial for evaluating the performance of biomarker assays implemented in the context of clinical studies, but oHow to evaluate the parallelism of a method for biomarkers that are non-detectable in healthy donors (HD)? oDoes the selectivity of the recombinant protein in the biological matrix reflect the endogenous biomarker? oHow does the stability of the recombinant protein compare with endogenous biomarker? oCan you use incurred samples (informed consent, sufficient volume) for evaluating parallelism and stability? Methods To address these questions, we generated samples with endogenous biomarkers, named MAQC, by spiking supernatants of stimulated PBMC in the serum or plasma from HD. Three to four levels of MAQC per cytokine were prepared and used to assess parallelism, selectivity and long-term stability (LTS) at -80°C of pro- and anti-inflammatory cytokines and chemokines by use of V-plex, S-plex kits from MSD and ELLA kits. For all these parameters, accuracy was determined, with a target acceptance of 70-130% of the nominal value for selectivity and LTS or upstream dilution for parallelism. Results We were able to generate serum and plasma reference samples with low- to high-range levels of Th1 (IFN-g, IL-12p70, IL-2, TNF-α, CCL-2), Th2 (IL-4, IL-13, IL-10), Th17 (IL-17A) and Proinflammatory (IL-6, IL-8, IL-1β) cytokines. Selectivity was acceptable for most cytokines, except for IL-13, IL-4, IL-17A and IL-6. For IL-6, a major interference was observed in some samples, likely due to the presence of soluble IL-6 receptor in the original serum sample. For the other 3 cytokines, interference, leading to a bias close to -30%, was observed that could not be lifted by diluting samples. For all cytokines but IL-13, endogenous diluted similarly as recombinant protein from calibrator. Twelve months LTS was demonstrated for all cytokines in MAQC and comparable to recombinant proteins spiked in human serum. Conclusion To conclude, reference samples with endogenous cytokines/chemokines can be produced from primary immune cells. These can be used to assess parallelism and long-term stability when sufficient volume of matrices with high enough concentrations are not available. These would be even more valuable if they could be commercially available for use as quality controls in validation and clinical studies.

CLINICAL CHARACTERISTICS AND SERUM CONCENTRATIONS OF SOME T-HELPER 2-DERIVED CYTOKINES IN PATIENTS WITH GENERALIZED ERYTHEMA MULTIFORME

Objective: To describe the clinical characteristics of patients with erythema multiforme (EM) presenting with generalized skin lesions and to investigate the serum concentrations of certain T-helper 2 (Th2) cytokines in these patients, exploring their correlation with specific clinical features. Subjects and Methods: This cross-sectional descriptive study included 33 patients diagnosed with EM featuring generalized skin lesions at the National Hospital of Dermatology and Venereology from April 2017 to August 2019. Additionally, 32 healthy controls (HCs) participated as the control group. Clinical examinations, medical history interviews, and serum sample collections were conducted for all subjects. The fluorescence covalent microbead immunosorbent assay technique was used to detect multiple cytokines simultaneously: IL-4, IL-5, and IL-13. The Mann-Whitney U test compared the serum cytokine levels between the two groups, with statistical significance set as p&lt;0.05. Pearson's test was applied to evaluate the correlation between two quantitative variables. Results: The mean age of EM patients with generalized lesions was 42.2 years; 30.3% were male, and 69.7% were female. Twenty-two patients (66.7%) had an illness duration of less than one week—a history of medication use before illness onset was reported by 60.6% of patients. Only 15.2% of patients had mucosal lesions. In the EM group, serum levels of IL-4 and IL-5 were 1.55±4.35 pg/ml and 7.12±18.91 pg/ml, respectively, which were lower than those in the HCs group (9.15±10.17 pg/ml and 21.38±20.85 pg/ml, respectively), p&lt;0.001. Serum IL-13 levels were identical in both groups (1.48 pg/ml). No correlation was found between serum IL-4 levels and age (r=0.08; p&gt;0.05), nor between serum IL-5 levels and age (r=-0.055; p&gt;0.05). Conclusion: Th2 cytokine levels in the EM group with generalized skin lesions were lower compared to the HCs group, with no correlation between these cytokine levels and age. Th2 is likely not an important factor in the pathogenesis of generalized EM. Received: 16 May 2023Revised: 24 June 2023Accepted: 22 July 2023

Th17 and T Regulatory Cytokines in Serum, Lesional Skin, and Stimulated Peripheral Blood Mononuclear Cell Culture Supernatants from Type 1 Leprosy Reaction Patients.

There are conflicting reports regarding the roles of T helper-17 (Th17) and T regulatory (Treg) cells in type 1 leprosy reactions (T1Rs). Also, literature on the correlation of immunological parameters with a validated scoring system and the effect of treatment on cytokines is lacking. Adult patients with untreated T1R and nonreactional spectrum-matched controls were included in the study for comparison of levels of Th17 and Treg pathway cytokines in serum, skin lesions (reactional), and peripheral blood mononuclear cells (PBMCs) culture supernatants. Venous blood samples were collected at baseline and after resolution of reaction (post treatment with nonsteroidal anti-inflammatory drugs [NSAIDs] or steroids) for serum cytokine estimation and PBMC stimulation assays, and lesional (reactional) skin biopsy for cytokine messenger RNA (mRNA) estimation. Thirty-two cases of T1R were recruited (23 patients completed follow-up). Serum levels of cytokines were not significantly different between cases and controls or between pre- and post-treatment samples. Tissue mRNA and Mycobacterium leprae (M. leprae) antigen-stimulated PBMC culture supernatant levels of Interleukin (IL)-17A, IL-17F, IL-6, and IL-23 were significantly higher in T1R than in controls. Levels of IL-10 and Transforming Growth Factor-beta (TGF-β) were comparable among the two groups. The levels of all cytokines were significantly reduced after treatment. There was no significant difference in magnitude of the fall between those treated with steroids versus NSAIDs. This study suggests heightened Th17 response in T1R, with a prominent inability of the regulatory cytokines IL-10 and TGF-β to control the associated inflammation. The dynamics of change after resolution of T1R were comparable between NSAID and oral steroid treatment groups.

Integration of Immune Responses and Transcriptomic Signatures Reveals the Efficacy of Maternal Genetic Vaccination in a Pregnant Model and Its Neonates.

Maternal vaccination is essential for safeguarding both mother and foetus from infectious diseases. This study investigated the immunogenicity and efficacy of a maternal ORF-B2L genetic vaccine in a pregnant rat model, focusing on maternal-neonatal immune modulation, placental and neonatal spleen transcriptomics and the underlying mechanisms contributing to neonatal immune development. Female rats received intramuscular injections of either a gene vaccine (GV) containing 200 μg of recombinant ORF-B2L DNA and 50 μg of a subunit protein or an empty plasmid as a control. Results showed significantly higher levels of specific anti-B2L antibodies and Th1 and Th2 cytokine levels in both maternal and neonatal sera from the GV group compared to the control group (p < 0.05). Transcriptome analysis identified 1295 differentially expressed genes (DEGs) in the placenta and 998 DEGs in the neonatal spleen, with upregulated pathways associated with immune cell recruitment, cytokine signalling and hormone regulation in the GV group. Notably, upregulated DEGs such as TLR4, ESR1 and various cytokine/chemokine-related genes in the placenta suggest enhanced immune regulation and foetal protection. In the neonatal spleen, increased expression of IL-1β, IL-6, IL-10 and CD69 indicates enhanced T and B cell development and pathogen defence. The upregulation of IL-1β suggests a Th1 response, while elevated IL-10 indicates a potential Th2-biased immunity, reflecting a balanced Th1/Th2 response that is crucial for effective adaptive immunity. Overall, maternal ORF-B2L genetic vaccination induces a robust immune response, enhancing maternal-foetal protection and shaping neonatal immune responses, offering valuable insights for optimizing maternal vaccination strategies.

Polyphenol oxidase cross-linking enhances whey protein-induced systemic food allergy by regulating miRNA in CD4+ T cells.

Whey protein (WP) contains two major allergenic proteins, α-lactalbumin and β-lactoglobulin, which significantly impact its incorporation and application in food products. Current research primarily focuses on the dynamic changes in allergenicity during the processing of individual protein components. To simulate realistic conditions in food processing, this study aims to investigate the effect of polyphenol oxidase cross-linking on the allergenicity of complex protein matrices. Our findings indicate that mice receiving polyphenol oxidase-crosslinked WP (CL-WP) exhibited more severe systemic food allergic reactions, characterized by decreased body temperature and significantly increased serum levels of specific IgE and mMCPT-1 compared to the WP group. Furthermore, mice in the CL-WP group displayed more pronounced intestinal injury. Flow cytometry results showed a significant decrease in CD103+MHC-II+CD11c+ cells and a significant increase in the proportion of Th2 cells in the CL-WP group. Simultaneously, the marked elevation of Th2 cytokine levels in spleen cell supernatants further indicated a significant Th2 bias in these mice. Lastly, miRNA sequencing of CD4+ T cells from the spleen revealed that among the differentially expressed miRNAs, miR-532-5p was significantly upregulated in both WP and CL-WP groups compared to controls, while miR-322-3p was downregulated in both groups. miR-27a-5p remained unchanged in the WP group but was significantly downregulated in the CL-WP group, and miR-92a-3p was upregulated in the WP group but unchanged in the CL-WP group. These results suggest that miRNAs may serve as potential biomarkers for the severity of milk allergy.

Maternal aspartame exposure alters lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.

Maternal aspartame exposure alters lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.

SPA14 liposomes combining saponin with fully synthetic TLR4 agonist provide adjuvanticity to hCMV vaccine candidate

In the aim of designing and developing a novel saponin-based adjuvant system, we combined the QS21 saponin with low microgram amounts of the fully synthetic TLR4 agonist, E6020, in cholesterol-containing liposomes. The resulting adjuvant system, termed SPA14, appeared as a long-term stable and homogeneous suspension of mostly unilamellar and a few multilamellar vesicles, with an average hydrodynamic diameter of 93 nm, when formulated in citrate buffer at pH 6.0-6.5. When compared in an in vitro human innate immunity construct to AS01B, the QS21/MPL® liposomal adjuvant system of GSK, and with QS21-Liposomes used as benchmarks, SPA14 displayed the strongest immunostimulatory potential based on antigen-presenting cell (APC) activation and cytokine secretion, which was essentially driven by the highly active E6020 agonist in this assay. When tested as an adjuvant in vivo with human cytomegalovirus glycoprotein B (gB) and pentamer complex (PC) as test antigens, SPA14 was generally well tolerated and as active as AS01B for the induction of long-lasting CMV-neutralizing antibodies in mice and non-human primates (NHPs). Both adjuvants promoted the induction of Th-1 responses based on IgG2c production in mice and IFN-γ production in mice and NHPs, but in mice, a higher level of Th-2 cytokines (IL-5) and higher IgG1 over IgG2c secreting cells ratios were obtained with SPA14 indicating that the adjuvant profile of SPA14 could be less Th-1 biased than that of AS01B. From a developability standpoint, SPA14 could be manufactured by a simple and scalable ethanol injection method, owing to the high solubility in ethanol of all its lipidic components, including E6020. Furthermore, E6020 is a single molecule, well-characterized fully synthetic TLR4 agonist constructed in eight synthetic steps from entirely crystalline starting materials and intermediates via an optimized high-yield synthetic route. Overall, our data suggest that SPA14 is a viable, easy-to-manufacture, potent novel adjuvant system that could be broadly applicable as a ready-to-mix adjuvant in the form of a long-term stable liquid formulation.

Sex-specific cytokine, chemokine, and growth factor signatures in T1D patients and progressors.

Numerous studies have reported altered cytokine levels in type 1 diabetes (T1D) patients, yet findings remain inconsistent. In this pilot study, we tested the hypothesis that circulating immune markers exhibit sex-based differences in T1D, both prior to and after disease onset. We analyzed 47-48 cytokine, chemokine, and growth factor levels in two cohorts. To assess post-disease differences, we analyzed serum samples from 25 controls and 25 T1D patients. To examine pre-disease progression, we utilized samples from 21 control children and 16 T1D progressors, collected at age 5 years before disease onset. Across all T1D patients and controls, only macrophage colony-stimulating factor and interleukin (IL)-6 showed significant differences. However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Female T1D patients exhibited lower levels of inflammatory cytokines (tumor necrosis factor-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (macrophage inflammatory protein (MIP)-1α, regulated upon activation, normal T cell expressed and secreted, MIP-3) compared to female controls, differences that were not observed in males. Notably, IL-22 was lower in female T1D patients compared to female controls, whereas it was higher in male T1D patients compared to male controls. Male T1D patients showed elevated levels of growth factors (epidermal growth factor, platelet-derived growth factor-AB/BB) compared to male controls. In T1D progressors, growth-regulated alpha was lower compared to controls in both sexes. Multiple regression analysis further revealed associations between cytokine levels and factors such as age, BMI, and breastfeeding duration. Overall, our findings serve as a proof of concept, highlighting the importance of sex-specific differences in T1D pathogenesis. However, follow-up studies with larger sample sizes are needed to validate and generalize these results.

Association of systemic inflammation and long-term dysfunction in COVID-19 patients: A prospective cohort.

Association of systemic inflammation and long-term dysfunction in COVID-19 patients: A prospective cohort.

Age-specific dynamics of neutralizing antibodies, cytokines, and chemokines in response to La Crosse virus infection in mice.

La Crosse virus (LACV) is a primary cause of pediatric arboviral encephalitis in the United States, particularly affecting children aged 16 years or younger. This age-related susceptibility extends to murine models, where weanling mice (3 weeks old) succumb to LACV infection, while adults (≥6 weeks old) demonstrate resistance. Despite its clinical relevance, the host immune response to LACV is not fully understood. In this study, we investigated the roles of neutralizing antibodies (nAbs), cytokines, and chemokines in weanling and adult mice following infection with 5 × 105 plaque-forming units (PFU) of LACV. Weanling mice demonstrated early disease onset with elevated peripheral viremia, but passive transfer of adult serum, confirmed to have nAbs, to naïve weanlings prior to infection completely rescued them from death. Moreover, adult mice had increased Th1 cytokines, Th9/Th17/Th22/Treg cytokines, and many chemokines. In contrast, weanlings had higher Th2 cytokines, correlating with symptoms onset. Flow cytometry and intracellular cytokine staining further demonstrated that weanling mice produced higher levels of IL-4 by CD4+ and CD8+ T cells compared to adults, regardless of infection status. Conversely, LACV-infected adult mice had increased IFN-γ production by CD8+ T cells compared to uninfected controls. Finally, the adoptive transfer of splenocytes from immune adult mice to naïve weanlings delayed neurological symptoms and improved survival. In conclusion, this study links nAbs and cytokine and chemokine responses to protective immunity in adult mice, contrasting with the pathogenesis seen in weanlings. These findings underscore the importance of further research into innate and adaptive immune mechanisms during LACV infection.IMPORTANCELa Crosse virus (LACV) is a primary cause of pediatric encephalitis in the United States, with an impact on children aged 16 years or younger. This age-related susceptibility is recapitulated in mouse models, where young mice succumb to LACV-induced disease, while adults demonstrate resistance. Our understanding of host responses to LACV remains underexplored. This study sheds light on the dynamics of neutralizing antibodies (nAbs), cytokines, and chemokines following LACV infection in both adult and weanling mice. Our study reveals age-specific variations in viremia, neutralizing antibody titers, survivability, and levels of cytokines and chemokines. Adult mice exhibit significantly elevated levels of Th1 cytokines, contrasting with elevated levels of Th2 cytokines observed in weanling mice, often coinciding with the onset of symptoms. These data reveal age-specific dynamics in cytokines and chemokines associated with protective versus pathogenic immunity, emphasizing the need for further studies on innate and adaptive immunity.