IL-6 Cytokines Research Articles

The in vitro and in vivo anti-inflammatory and anti-oxidative effects of an amino acid blend supplemented feed on pigs experimentally challenged with Salmonella Typhimurium.

The in vitro and in vivo anti-inflammatory and anti-oxidative effects of an amino acid (AA) blend (tryptophan, threonine, and methionine) in pigs. This study aimed to evaluate the in vitro anti-inflammatory and anti-oxidative effects of an AA blend on intestinal porcine epithelial cells (IPEC-J2) and the in vivo anti-inflammatory and anti-oxidative effects in pigs experimentally challenged with Salmonella Typhimurium. IPEC-J2 were pretreated with an AA blend for 25 h and then treated with lipopolysaccharide (LPS), deoxynivalenol (DON), or H2O2 for in vitro evaluation. A controlled standard diet supplemented with 0.3% of the AA blend was orally fed to the treated group pigs for 14 days, beginning at 21 days of age. At the end of the feeding period, pigs were orally inoculated with Salmonella Typhimurium. Pre-treatment with the AA blend reduced LPS/DON-induced interleukin (IL)-8 mRNA as a measurement of the anti-inflammatory effect and H2O2-induced reactive oxygen species (ROS) as a measurement of the anti-oxidative effect on IPEC-J2. Feeding with an AA blend resulted in a reduction of proinflammatory (tumor necrosis factor-α, IL-6, and IL-8) cytokine levels, while treated pigs experienced an increase in anti-inflammatory IL-10 cytokine in their sera. The addition of an AA blend-supplemented pig feed resulted in significantly lower Salmonella-induced cecal lesion scores compared to untreated pigs. Supplementation of feed with an AA blend reduced intestinal inflammation and pathology in pigs and may be applied for the control of Salmonella Typhimurium infection, as demonstrated in this study.

Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization.

Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF). DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats' joints on the seventh day (inflammatory phase). Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.

Exploring the health-promoting potential: Dietary intervention with live or inactivated Lactobacillus gasseri HM1 probiotics in obese mice

BackgroundThis study explores the impact of dietary interventions with live or inactivated Lactobacillus gasseri HM1 probiotics on metabolic health in mice. MethodsAfter inducing obesity in 24 mice with a high-fat diet, they transitioned to a standard chow diet (SCD) while receiving a daily oral placebo, live HM1, heat-killed HM1 (HK-HM1), or sonication-killed HM1 (SK-HM1) for 6 weeks. ResultsResults indicate that SCD with live HM1 significantly improved triglyceride levels, glucose tolerance, and insulin sensitivity. SK-HM1 improved perirenal fat inflammation and reduced serum leptin concentration, while HK-HM1 showed improvements in inflammation in fat tissues and reduced serum IL-6, leptin, and catalase protein levels. Both HK-HM1 and SK-HM1 reduced colon IL-6, TGF-β1, and IL-1β cytokine levels, with HK-HM1 having the most significant effect. ConclusionsThese findings underscore the potential of dietary interventions with HM1 probiotics to enhance metabolic health, revealing distinct benefits between live and inactivated forms.

Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria.

Research regarding the role of the IL-12 cytokine family in modulating immune and inflammatory responses is continuously evolving. In this study, the contribution of the p35 and p40 subunits as monomers (noted as IL-12p35 and IL-12p40) and heterodimers (noted as IL-12p70 or IL-12p35/p40) was analysed in the pathophysiology and progression of chronic spontaneous urticaria (CSU). We conducted a longitudinal, case-control study involving 42 CSU cases and 40 control cases comprising adults without associated conditions. Serial measurements were performed to assess the serum levels of IL-12p70, IL-12p35, and IL-12p40 at the onset of the disease (pre-therapy phase) and 6 weeks after the initiation of the treatment (post-therapy phase). During the pre-therapeutic phase of CSU, elevated serum levels of IL-12 cytokine subtypes were detected compared to the control group. The relationship between IL-12 profiles and the course of CSU highlighted the pro-inflammatory role of IL-12p70 and the anti-inflammatory role of IL-12p35. Significant correlations were observed between IL-12p70 levels and the duration of the disease, as well as between IL-12 and the effectiveness of H1-antihistamines. The molecular background for the pleiotropic activities mediated by IL-12-derived cytokines in patients with CSU lies in the strict regulation of the production, signalling pathways, and cytokine-specific influences on the same pathophysiological events. The results of the present study suggest that the superficial layers of the skin serve as a cellular source of IL-12, a cytokine produced through antigenic stimulation. In patients with CSU, we identified independent, additive, or divergent functions of IL-12p70, IL-12p35, and IL-12p40, all relevant to systemic inflammation. These findings prove that the prototype programming of IL-12 is abnormal in CSU.

Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence.

Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4+ and CD8+ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells.

Structural characterization and ferroptosis-related immunomodulatory of a novel exopolysaccharide isolated from marine fungus Aspergillus medius

Marine fungal exopolysaccharides play a crucial role in immunoregulation. In this investigation, a novel polysaccharide was extracted from the culture medium of the marine fungus Aspergillus medius SCAU-236. Compositional analysis revealed a structure composed of glucose units with (1,4)-α-D-Glcp, (1,3,4)-β-D-Glcp, and (1,4,6)-α-D-Glcp, along with side chains of 1-α-D-Glcp linked to carbon 6 of (1,4,6)-α-D-Glcp and carbon 3 of (1,3,4)-β-D-Glcp. Functional evaluations on RAW264.7 macrophage cells demonstrated Aspergillus medius polysaccharide (ASMP)'s effects on cell proliferation, nitric oxide levels, and the secretion of TNF-α, IL-6, and IL-1β cytokines. Additionally, metabolomics indicated ASMP's potential to modulate macrophage immune function by impacting key regulatory molecules, including COX-2, iNOS, Nrf2, SLC7A11, GPX4, and ACSL4. The Nrf2/SLC7A11/GPX4 axis and ACSL4 were suggested to be involved in ASMP-induced ferroptosis, leading to increased reactive oxygen species (ROS) levels and lipid peroxidation. These findings propose a unique mechanism by which ASMP exerts immunomodulatory effects through ferroptosis induction, contributing to the understanding of marine-derived compounds in immunomodulation research.

Human neutrophils drive skin autoinflammation by releasing interleukin (IL)-26.

Autoinflammation is a sterile inflammatory process resulting from increased neutrophil infiltration and overexpression of IL-1 cytokines. The factors that trigger these events are, however, poorly understood. By investigating pustular forms of psoriasis, we show that human neutrophils constitutively express IL-26 and abundantly release it from granular stores upon activation. In pustular psoriasis, neutrophil-derived IL-26 drives the pathogenic autoinflammation process by inducing the expression of IL-1 cytokines and chemokines that further recruit neutrophils. This occurs via activation of IL-26R in keratinocytes and via the formation of complexes between IL-26 and microbiota DNA, which trigger TLR9 activation of neutrophils. Thus our findings identify neutrophils as an important source of IL-26 and point to IL-26 as the key link between neutrophils and a self-sustaining autoinflammation loop in pustular psoriasis.

Immunocytokines with target cell-restricted IL-15 activity for treatment of B cell malignancies.

Despite the advances in cancer treatment achieved, for example, by the CD20 antibody rituximab, an urgent medical need remains to optimize the capacity of such antibodies to induce antibody-dependent cellular cytotoxicity (ADCC) that determines therapeutic efficacy. The cytokine IL-15 stimulates proliferation, activation, and cytolytic capacity of NK cells, but broad clinical use is prevented by short half-life, poor accumulation at the tumor site, and severe toxicity due to unspecific immune activation. We here report modified immunocytokines consisting of Fc-optimized CD19 and CD20 antibodies fused to an IL-15 moiety comprising an L45E-E46K double mutation (MIC+ format). The E46K mutation abrogated binding to IL-15Rα, thereby enabling substitution of physiological trans-presentation by target binding and thus conditional IL-15Rβγ stimulation, whereas the L45E mutation optimized IL-15Rβγ agonism and producibility. In vitro analysis of NK activation, anti-leukemia reactivity, and toxicity using autologous and allogeneic B cells confirmed target-dependent function of MIC+ constructs. Compared with Fc-optimized CD19 and CD20 antibodies, MIC+ constructs mediated superior target cell killing and NK cell proliferation. Mouse models using luciferase-expressing human NALM-6 lymphoma cells, patient acute lymphoblastic leukemia (ALL) cells, and murine EL-4 lymphoma cells transduced with human CD19/CD20 as targets and human and murine NK cells as effectors, respectively, confirmed superior and target-dependent anti-leukemic activity. In summary, MIC+ constructs combine the benefits of Fc-optimized antibodies and IL-15 cytokine activity and mediate superior NK cell immunity with potentially reduced side effects. They thus constitute a promising new immunotherapeutic approach shown here for B cell malignancies.

Association of Tumor Necrosis Factor-Alpha, Interleukin-1β, Interleukin-8, and Interferon-γ with Obstructive Sleep Apnea in Both Children and Adults: A Meta-Analysis of 102 Articles.

Background: Cytokines may have a significant impact on sleep regulation. In this meta-analysis, we present the serum/plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, IL-1β, and interferon-gamma (IFN-γ) in both children and adults with obstructive sleep apnea (OSA) in comparison to controls. Methods: Four electronic databases were systematically searched (PubMed, Web of Science, Scopus, and Cochrane Library) through 19 October 2023, without any restrictions on language, date, age, and sex. We used Review Manager version 5.3 to perform meta-analysis and presented the data as standardized mean difference (SMD) and 95% confidence interval (CI) values to evaluate the relationships between the levels of cytokines and OSA. Results: A total of 102 articles (150 independent studies) were included in the meta-analysis. The pooled SMDs in adults were 1.42 (95%CI: 1.11, 1.73; p < 0.00001), 0.85 (95%CI: 0.40, 1.31; p = 0.0002), 0.69 (95%CI: 0.22, 1.16; p = 0.004), and 0.39 (95%CI: -0.37, 1.16; p = 0.31) for TNF-α, IL-8, IL-1β, and IFN-γ, respectively. The pooled SMDs in children were 0.84 (95%CI: 0.35, 1.33; p = 0.0008), 0.60 (95%CI: 0.46, 0.74; p < 0.00001), 0.25 (95%CI: -0.44, 0.93; p = 0.49), and 3.70 (95%CI: 0.75, 6.65; p = 0.01) for TNF-α, IL-8, IL-1β, and IFN-γ, respectively. Conclusions: The levels of proinflammatory cytokines of TNF-α, IL-8, and IL-1β in adults, and TNF-α, IL-8, and IFN-γ in children with OSA, are significantly higher than those in controls.

Investigating the association between the tissue expression of miRNA-101, JAK2/STAT3 with TNF-α, IL-6, IL-1β, and IL-10 cytokines in the ulcerative colitis patients.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by numerous factors, such as immune system dysfunction and genetic factors. MicroRNAs (miRNAs) play a crucial role in UC pathogenesis, particularly via the JAK-STAT pathway. Our aim was to investigate the association between miRNA-101 and JAK2-STAT3 signaling pathway with inflammatory cytokines in UC patients. We enrolled 35 UC patients and 35 healthy individuals as the control group, referred to Shariati Hospital, Tehran, Iran. Patients were diagnosed based on clinical, laboratory, histological, and colonoscopy criteria. RNA and protein extracted from tissue samples. Real-time PCR was used to assess the expression levels of miRNA-101, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 genes, while western blot was employed to measure levels of P-STAT3, total STAT3, and JAK2 proteins. Expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 significantly increased, while the expression of IL-10 significantly decreased in the case group versus controls. Additionally, miRNA-101 expression was significantly higher in UC patients. A significant correlation between miRNA-101 and IL-6 expression was observed, indicating their relationship and possible impact on cell signaling pathways, JAK2-STAT3. No significant changes were observed in phosphorylated and total STAT3 and JAK2 protein expression. This study provides evidence of increased miRNA-101 expression in UC tissue, suggesting a potential correlation between miRNA-101 and IL-6 expression and their involvement in the JAK2-STAT3 pathway. The study confirms alterations in UC patients' pro-inflammatory cytokines and anti-inflammatory IL-10. However, further investigations are needed to understand the exact role of miRNA-101 in UC pathogenesis fully.

Gochujang, a traditional Korean fermented food, protects through suppressed inflammatory pathways and histological structure disruption in dextran sodium sulfate (DSS)-induced colitis mice

The mechanisms underlying chronic inflammatory diseases remain unclear. Therefore, researchers have explored the mechanisms underlying colitis using diverse materials. Recently, there has been an increasing interest in fermented products and bioconversion materials, their potential efficacy is being actively studied. Gochujang, a traditional Korean fermented product, is crafted by blending fermented Meju powder, gochu (Korean chili) powder, glutinous rice, and salt. In our study, we explored the effectiveness of Gochujang (500 mg/kg; Cheongju and Hongcheon, Korea) in dextran sulfate sodium (DSS)-induced colitis mice model. Gochujang was orally administered for 2 weeks, followed by the induction of colitis using 3% DSS in the previous week. During our investigation, Gochujang variants (TCG22-25, Cheongju and TCG22-48, Hongcheon) did not exhibit significant inhibition of weight reduction (p = 0.061) but notably (p = 0.001) suppressed the reduction in large intestine length in DSS-induced colitis mice. In the serum from colitis mice, TCG22-48 demonstrated reduced levels of the inflammatory cytokines interleukin (IL)-6 (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.001). Additionally, it inhibited the phosphorylation of Erk (p = 0.028), p38, and NF-κB (p = 0.001) the inflammatory mechanism. In our study, TCG22-25 demonstrated a reduction in the IL-6 level (p = 0.001) in serum and inhibited the phosphorylation of p38 and NF-κB (p = 0.001). Histological analysis revealed a significant (p = 0.001) reduction in the pathological score of the large intestine from TCG22-25 and TCG22-48. In conclusion, the intake of Gochujang demonstrates potent anti-inflammatory effects, mitigating colitis by preventing the large intestine length reduction of animals with colitis, lowering serum levels of TNF-α and IL-6 cytokines, and inhibiting histological disruption and inflammatory mechanism phosphorylation.

Blood Level of Nitric Oxide Metabolites and Expression of Genes Regulating NO Synthesis in Early Forms of Non-Alcoholic Fatty Liver Disease.

The levels of NO metabolites in the plasma and mRNA of the NOS3, ATG9B, and NOS2 genes in peripheral blood leukocytes of healthy people and patients with early forms of non-alcoholic fatty liver disease (steatosis and weak activity non-alcoholic steatohepatitis) were studied. In patients with steatohepatitis, the concentration of NO metabolites in the blood and the level of mRNA of the NOS2 gene were higher than in patients with steatosis and healthy people. These differences can be of diagnostic value for distinguishing between steatosis and weak activity steatohepatitis in non-alcoholic fatty liver disease. A correlation between the levels of NO metabolites and the expression of the NOS2 gene in weak activity steatohepatitis was established, which indicates activation of NO synthesis in non-alcoholic steatohepatitis due to the expression of the inducible NO synthase gene. The level of the NOS2 gene mRNA in peripheral blood leukocytes of patients with weak activity steatohepatitis correlated with the level of TNFα and IL-6 cytokines. An increase in the level of NO in the blood in weak activity steatohepatitis correlated with the level of MDA, an indicator of oxidative stress.

Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Prophylactic and Therapeutic Efficacy of Ultrasonicated Rosmarinus officinalis Ethanolic Extract and its Chitosan-Loaded Nanoparticles Against Eimeria tenella Infected Broiler Chickens

PurposeThe in vivo efficacy of ultrasonicated Rosmarinus officinalis ethanolic extract (UROEE) and its chitosan-loaded nanoparticles (UROEE-CsNPs) was investigated as a dietary prophylactic agent and as a therapeutic treatment against Eimeria tenella infected broiler chickens.MethodsChickens were infected with 4 × 104E. tenella oocysts at 21 days old for primary infection and with 8 × 104 oocysts at 35 days old for secondary infection. Eleven experimental groups were conducted. Dietary addition of 100 mg/kg UROEE and 20 mg/kg for CsNPs as well as UROEE-CsNPs were included for prophylactic groups from day 1 to 42. The same doses were used for therapeutic treatment groups for 5 constitutive days. Oocyst output in feces was counted. Histopathological and immunohistochemical studies were conducted. Gene expression of pro-inflammatory cytokines as IFN-γ, IL-1β and IL-6 as well as anti-inflammatory cytokines as IL-10 and TGF-β4 was analyzed using semi-quantitative reverse transcriptase-PCR.ResultsThe results showed an efficacy of UROEE, CsNPs and UROEE-CsNPs in reduction of oocyst excretion and improving the cecal tissue architecture. CD4+ and CD8+ T lymphocytes protein expression were reduced. E. tenella infection lead to upregulation of pro-inflammatory cytokines as IFN-γ, IL-1β, IL-6 and anti-inflammatory cytokines as TGF-β4 following primary infection, while their expression was downregulated following secondary infection.ConclusionThe dietary prophylactic additives and therapeutic treatments with UROEE, CsNPs and UROEE-CsNPs could decrease the inflammatory response to E. tenella as indicated by oocyst output reduction, histopathological improvements, CD4+ and CD8+ T cells protein expression reduction as well as reducing mRNA expression levels of the tested cytokines following primary and secondary infections. Consequently, these results will help to develop better-combating strategies for the control and prevention of coccidiosis on poultry farms as a dietary prophylactic agent or as a therapeutic treatment.Graphical

Strain specific differences in vitamin D3 response: impact on gut homeostasis.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects.

Tapak Liman (Elephantopus scaber L.) Leaves Ethanol Extract Improves the Production of IL-6 and IL-17 Cytokines in Mice with Bleomycin-induced Pulmonary Fibrosis

Tapak Liman (Elephantopus scaber L.) Leaves Ethanol Extract Improves the Production of IL-6 and IL-17 Cytokines in Mice with Bleomycin-induced Pulmonary Fibrosis

Altered COVID-19 immunity in children with asthma by atopic status

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Strain-Specific Anti-Inflammatory Effects of Faecalibacterium prausnitzii Strain KBL1027 in Koreans.

Faecalibacterium prausnitzii is one of the most dominant commensal bacteria in the human gut, and certain anti-inflammatory functions have been attributed to a single microbial anti-inflammatory molecule (MAM). Simultaneously, substantial diversity among F. prausnitzii strains is acknowledged, emphasizing the need for strain-level functional studies aimed at developing innovative probiotics. Here, two distinct F. prausnitzii strains, KBL1026 and KBL1027, were isolated from Korean donors, exhibiting notable differences in the relative abundance of F. prausnitzii. Both strains were identified as the core Faecalibacterium amplicon sequence variant (ASV) within the healthy Korean cohort, and their MAM sequences showed a high similarity of 98.6%. However, when a single strain was introduced to mice with dextran sulfate sodium (DSS)-induced colitis, KBL1027 showed the most significant ameliorative effects, including alleviation of colonic inflammation and restoration of gut microbial dysbiosis. Moreover, the supernatant from KBL1027 elevated the secretion of IL-10 cytokine more than that of KBL1026 in mouse bone marrow-derived macrophage (BMDM) cells, suggesting that the strain-specific, anti-inflammatory efficacy of KBL1027 might involve effector compounds other than MAM. Through analysis of the Faecalibacterium pan-genome and comparative genomics, strain-specific functions related to extracellular polysaccharide biosynthesis were identified in KBL1027, which could contribute to the observed morphological disparities. Collectively, our findings highlight the strain-specific, anti-inflammatory functions of F. prausnitzii, even within the same core ASV, emphasizing the influence of their human origin.

Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential.

Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family and has been widely recognized as a master regulator of type 2 inflammatory responses at barrier surfaces. Recent studies found dysregulation of the TSLP-TSLP receptor (TSLPR) pathway is associated with the pathogenesis of not only allergic diseases but also a wide variety of cancers including both solid tumors and hematological tumors. Thus, the blockade of TSLP represents an attractive therapeutic strategy for allergic diseases and cancer. In this study, we report the development of a novel humanized anti-TSLP monoclonal antibody (mAb) HZ-1127. Binding affinity, specificity, and ability of HZ-1127 in inhibiting TSLP were tested. HZ-1127 selectively binds to the TSLP cytokine with high affinity and specificity. Furthermore, HZ-1127 dramatically inhibits TSLP-dependent STAT5 activation and is more potent than Tezepelumab, which is an FDA-approved humanized mAb against TSLP for severe asthma treatment in inhibiting TSLP-induced CCL17 and CCL22 chemokines secretion in human peripheral blood mononuclear cells. Our pre-clinical study demonstrates that HZ-1127 may serve as a potential therapeutic agent for allergic diseases and cancer.

Bacillus coagulans regulates gut microbiota and ameliorates the alcoholic-associated liver disease in mice.

Alcoholic-associated liver diseases (ALD) are now widespread issues worldwide. Alcoholic-induced chronic dysbiosis of the gut microbiota is one of the factors in the pathophysiology of ALD. In this work, we employed a chronic-binge ethanol feeding mice model, as described in a previous report. Our findings demonstrate that hepatic inflammatory injury damage and accumulation of fat can be effectively reduced in mice with ALD by altering the gut microbiota utilizing Bacillus coagulans. Treatment with B. coagulans significantly modulates the levels of TNF-α, IL-1β, and IL-22 cytokines while maintaining tight junction proteins and mucin protein expressions to support intestinal barrier function restoration. Treatment with B. coagulans also alters the composition of the gut microbiota and increases the production of short-chain fatty acids (SCFAs). This is mostly due to B. coagulans promotes the growth of bacteria that produce SCFAs, such as Ruminococcus species and Akkermansia, while inhibiting the growth of pathogenic bacteria like Escherichia Shigella. Moreover, treatment with B. coagulans causes levels of 2-Ketobutyric acid, ketoleucine, and indoleacetic acid increase while homovanillic acid and 3'-O-Methylguanosine metabolites decrease significantly. This study facilitates the development of therapeutic and preventive strategies for ALD using lactic acid bacteria.