Brain, behavior, & immunity - health最新文献

{"title":"Networks and clusters of immunometabolic biomarkers and depression-associated features in middle-aged and older community-dwelling US adults with and without depression","authors":"Asma Hallab ,&nbsp;The Health and Aging Brain Study (HABS-HD) Study Team","doi":"10.1016/j.bbih.2025.101103","DOIUrl":"10.1016/j.bbih.2025.101103","url":null,"abstract":"<div><h3>Introduction</h3><div>Therapy-resistant depression is associated with higher levels of systemic inflammation and increased odds of metabolic disorders. It is, therefore, crucial to identify the biomarkers of high-risk individuals and understand the key features of depression-immunometabolic networks.</div></div><div><h3>Methods</h3><div>The multiethnic ≥50-year-old study population is a subset of the Health and Aging Brain Study: Health Disparities (HABS-HD) study. Spearman's rank correlation network analysis was performed between immunological, metabolic, and subscales of the Geriatric Depression Scale (GDS). Significant correlations were then evaluated using a multivariable linear regression analysis, including testing for non-linearity and clinical cutoffs.</div></div><div><h3>Results</h3><div>Two clusters were formed: the first included the immunometabolic biomarkers, and the second included the different subscales of GDS. The two clusters were significantly correlated at six edges. IL-6 and HbA1c were significantly correlated with anhedonic and melancholic features. Abdominal circumference and BMI were significantly correlated with anhedonic features. In the subgroup without current depression, IL-6 and Abdominal circumference maintained a significant edge with anhedonic features. TNF-alpha/melancholia and IL-6/cognitive concerns were additional relevant edges in older adults. The observed correlations remained statistically significant in the confounder-adjusted regression analysis and followed specific patterns.</div></div><div><h3>Conclusions</h3><div>Symptom clustering showed its superiority over relying on dichotomized depression diagnoses for identifying relevant immunometabolic biomarkers. This study is a first step toward understanding the particularities of immunometabolic depression for better risk stratification and to direct personalized preventive and therapeutic strategies in multiethnic aging populations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101103"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral infections and risk of mental illness: A Mendelian randomization study","authors":"Jian-Wei Huang ,&nbsp;Yi-Fei Wang ,&nbsp;Miao Tang ,&nbsp;Qian-Qian Cui ,&nbsp;Ying Guo ,&nbsp;Shuang-Qi Gao","doi":"10.1016/j.bbih.2025.101104","DOIUrl":"10.1016/j.bbih.2025.101104","url":null,"abstract":"<div><h3>Background</h3><div>Prior epidemiological evidence suggests associations between viral infections and psychiatric disorders, yet causal relationships remain insufficiently characterized. This study aims to investigate potential causal links using genetic instrumental variables.</div></div><div><h3>Methods</h3><div>A two-sample Mendelian randomization (MR) analysis was conducted using pooled European-ancestry genomic data. Exposures included hepatitis B virus (HBV), human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human papillomavirus (HPV), and Epstein-Barr virus (EBV) infections. Outcomes encompassed generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), schizophrenia (SCH), major depressive disorder (MDD), and manic episodes. Causal estimates were primarily derived via inverse variance weighting (IVW), with robustness assessed through MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated via Cochran's Qstatistic, MR-Egger intercept, and sensitivity plots.</div></div><div><h3>Results</h3><div>HBV infection was associated with reduced GAD risk (OR = 0.94; 95 % CI [0.91, 0.97]; P = 0.0012). Similarly, HIV and SARS-CoV-2 infections exhibited protective effects against OCD (OR = 0.84; 95 % CI [0.72, 0.97]; P = 0.019 and OR = 0.78; 95 % CI [0.61, 0.99]; P = 0.039). HPV infection decreased SCH risk (OR = 0.84; 95 % CI [0.76, 0.92]; P = 0.0005). Conversely, EBV infection elevated MDD risk (OR = 1.00; 95 % CI [1.00, 1.01]; P = 0.0015). Sensitivity analyses confirmed minimal pleiotropy (Q &gt; 0.05; MR-Egger intercept P &gt; 0.1).</div></div><div><h3>Conclusions</h3><div>This MR analysis provides genetic evidence supporting causal roles of specific viral infections in psychiatric disorders. Findings underscore the clinical relevance of viral prevention strategies for mental health outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101104"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vegetable intake is associated with lower psychological stress via increased anti-inflammatory responses in pregnant women with chronic diseases","authors":"Rosa S. Wong ,&nbsp;Keith T.S. Tung ,&nbsp;Patrick Ip","doi":"10.1016/j.bbih.2025.101106","DOIUrl":"10.1016/j.bbih.2025.101106","url":null,"abstract":"<div><div>Women with chronic diseases are susceptible to inflammation and stress during pregnancy. Dietary factors such as vegetable consumption can influence the level of inflammation markers in the body, which research has shown to be associated with stress levels. This study examined the moderating role of vegetable intake in the association between chronic disease history and stress levels via anti-inflammatory cytokine interleukin-10 (IL-10) in pregnant women. We recruited 239 pregnant women from antenatal clinics and used an electronic food frequency questionnaire to survey their vegetable intake. Plasma samples were collected at enrollment and assayed for IL-10. Perceived stress scale was completed one month after the assessment of dietary intake. The relationships among chronic disease history, vegetable intake, IL-10 levels, and stress levels were explored using moderated mediation analysis. Pregnant women with chronic diseases demonstrated elevated stress levels and decreased IL-10 levels compared to those without chronic conditions. However, a significant interaction was observed between vegetable intake and chronic disease history in modulating IL-10 levels (B = 0.09, p = 0.007). Specifically, consuming vegetables was positively associated with IL-10 levels in women with chronic diseases, while this association was not observed in women without chronic conditions. When consuming high levels of vegetables, women with chronic diseases were found to experience lower stress levels than those without (B = −0.43; Boot SE = 0.28; LLCI = −1.06; ULCI = −0.01). It is crucial for pregnant women with chronic diseases to consume a vegetable-rich diet, which could benefit their mental health by potentially reducing inflammation during pregnancy.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101106"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated miR-1246 and miR-1253 link inflammatory protein markers in plasma to major depressive disorder in female adolescents","authors":"Kristine Johannessen ,&nbsp;Dušan Braný ,&nbsp;Dana Dvorská ,&nbsp;Michaela Krivošová ,&nbsp;Miloslav Oppa ,&nbsp;Igor Ondrejka ,&nbsp;Ján Strnádel ,&nbsp;Nikola Ferencová ,&nbsp;Ingrid Tonhajzerová ,&nbsp;Zuzana Danková ,&nbsp;Erika Halašová ,&nbsp;Juraj Mokrý ,&nbsp;Betina Elfving","doi":"10.1016/j.bbih.2025.101108","DOIUrl":"10.1016/j.bbih.2025.101108","url":null,"abstract":"<div><div>Major depressive disorder (MDD) in adolescents is a prevalent psychiatric condition worldwide with severe consequences. Growing evidence shows that microRNAs (miRNAs) regulate many processes hypothesized to be involved in the pathogenesis of MDD including inflammation, suggesting their suitability as biomarkers. Still, more research is needed regarding miRNAs as biomarkers and the role of inflammation in adolescents with MDD.</div><div>This study applied the NanoString nCounter technology to identify dysregulated miRNAs in plasma from hospitalized female adolescents with MDD compared to healthy controls, as well as before and after antidepressant treatment. A multiplexed immunoassay was also performed to assess the plasma levels of 27 inflammatory proteins. A total of 33 patients and 14 healthy controls were included in the study.</div><div>miR-1246 and miR-1253 were downregulated in female adolescents with MDD compared to healthy controls, suggesting their potential as diagnostic biomarkers. Additionally, miR-496 was downregulated with treatment, indicating its potential as a prognostic biomarker. Moreover, increased levels of PDGF-BB and IL-7 were seen in adolescents with MDD compared to healthy controls, while IL-9 and MIP-1β levels decreased with antidepressant treatment. Finally, the expression of specific miRNAs were found to correlate with the levels of several inflammatory proteins.</div><div>In summary, miR-1246, miR-1253, and miR-496 are suggested as potential diagnostic and prognostic biomarkers. Furthermore, this study contributes in more detail to our understanding of miRNAs, inflammation, and MDD in female adolescents.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101108"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory under siege: the cognitive costs of smoking and vaping","authors":"Brian G. Oliver ,&nbsp;Qi Wang ,&nbsp;Rochelle A. Yarak ,&nbsp;Tharathip Hikasem ,&nbsp;Catherine A. Gorrie ,&nbsp;Chenju Yi ,&nbsp;Hui Chen","doi":"10.1016/j.bbih.2025.101102","DOIUrl":"10.1016/j.bbih.2025.101102","url":null,"abstract":"<div><div>Memory function is critically essential across all life stages, yet it is increasingly compromised by exposure to airborne pollutants due to human behaviours. This review examines the adverse impacts of tobacco smoke and e-cigarette vapour on memory function, emphasising the risks to younger populations. Both pollutants are potent oxidants that induce oxidative stress and inflammatory responses in the brain, leading to synaptic injury and neuronal apoptosis. These processes compromise neuronal integrity and function, potentially resulting in early-onset dementia. Additionally, third-hand exposure to tobacco smoke and e-cigarette vapour, through re-exposure to toxic chemicals on surfaces or clothing, poses significant risks, especially to toddlers. Epigenetic mechanisms, including DNA methylation and histone modification, further exacerbate these effects by altering gene expression critical for brain development and function. This review highlights the necessity for further research to develop risk-reduction strategies to protect cognitive health from these pollutants.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101102"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes of cognitive functions and proinflammatory cytokines across the lifespan in latent Toxoplasma gondii infection","authors":"Patrick D. Gajewski ,&nbsp;Peter Bröde ,&nbsp;Maren Claus ,&nbsp;Klaus Golka ,&nbsp;Jan G. Hengstler ,&nbsp;Jörg Reinders ,&nbsp;Carsten Watzl ,&nbsp;Edmund Wascher ,&nbsp;Stephan Getzmann","doi":"10.1016/j.bbih.2025.101105","DOIUrl":"10.1016/j.bbih.2025.101105","url":null,"abstract":"<div><h3>Background</h3><div>Recent findings showed serious consequences of latent <em>T. gondii</em> infection on the central nervous system, leading to psychiatric, immunological and cognitive impairments. However, little is known about the temporal dynamics of the latent <em>T. gondii</em> infection in respect to immunological and cognitive changes across the adult life span. The present study aims at evaluating the course of cognitive changes across the adult life span in relation to latent <em>T. gondii</em> infection and the interplay with proinflammatory cytokines leading to chronic inflammation as a potential origin of the cognitive decline in infected adults.</div></div><div><h3>Methods</h3><div>In a double-blinded cross-sectional design, data of 218 seropositive and 475 seronegative adults aged between 20 and 88 years were compared regarding crucial cognitive domains: processing speed, working memory, immediate and delayed memory, sustained attention, and executive functions. In a subsample of up to 300 participants, concentrations of proinflammatory cytokines IL-6, IL-8, IL-18, and TNF-α were analyzed to evaluate their interaction with <em>T. gondii,</em> and to determine whether the cytokines interact in their effects on cognition across the lifespan.</div></div><div><h3>Results</h3><div>The results showed an interaction between age and <em>T. gondii</em> status, with a decline in cognitive performance in infected, relative to non-infected, older individuals, and the reversed pattern in young to middle-aged adults. Specifically, this pattern was evident in working memory, immediate and delayed recall, as well as switching ability. Age was associated with increased levels of proinflammatory cytokines, and reduced concentration of <em>T. gondii</em> antibodies. IL-6, IL-8 and TNF-α levels were negatively associated with <em>T. gondii</em> antibody level and cognitive performance. Finally, <em>T. gondii</em> interacted with IL-6, IL-8 and TNF-α, predicting superior performance in immediate and delayed memory tasks in younger adults with high levels of <em>T. gondii</em> IgG antibodies and cytokines, whereas <em>T. gondii</em> IgG antibody and cytokine levels played less of a role for these functions in older age.</div></div><div><h3>Conclusion</h3><div>The findings support a model of dynamically shifting effects of <em>T. gondii</em> and proinflammatory cytokines on the central nervous system and cognition with increasing age, suggesting positive effects of <em>T. gondii</em> infections in younger adults, and neuroinflammatory effects in older age presumably due to chronic inflammation. Given the high prevalence of latent toxoplasmosis in the general population and the growing population of older adults, these findings are of relevance for public health.</div></div><div><h3>Trial registration</h3><div>Clinicaltrials.gov NCT05155397.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101105"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory study of the dysregulation of age-related changes in neural/glial antigen 2 and neuroinflammation markers in individuals with major depression","authors":"Javier Vargas-Medrano,&nbsp;Diana Sotelo,&nbsp;Guadalupe Vidal Martínez,&nbsp;Peter M. Thompson","doi":"10.1016/j.bbih.2025.101107","DOIUrl":"10.1016/j.bbih.2025.101107","url":null,"abstract":"<div><div>Aging involves the alteration of the central nervous system myelin, which is produced by oligodendrocytes. These cells originate from oligodendrocyte precursor [neural/glial antigen 2 (NG2)] cells, which are influenced by neuroinflammatory processes. Neuroinflammatory activity contributes to accelerated aging in individuals with mental illnesses such as major depressive disorder (MDD). This study was conducted to better understand the anti- and pro-neuroinflammatory changes associated with NG2 cells in aging individuals with MDD. Human postmortem dorsolateral prefrontal cortex samples were obtained from adults with MDD and normal controls (NCs) of different ages. Western blotting was performed to measure the protein levels of the oligodendrocyte progenitor cell marker NG2, the inflammatory markers interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor (HGF), and the anti-inflammatory neuronal viability marker B-cell lymphoma 2 (Bcl-2). Age-related changes in these markers were examined by simple linear regression. In NCs, the levels of NG2 and HGF increased linearly with age (<em>p</em> = 0.04 and <em>p</em> = 0.02, respectively), and the Bcl-2 level tended to follow the same trend (<em>p</em> = 0.08). The IL-1β and TNF-α levels were not significantly associated with age in NCs (<em>p</em> = 0.96 and <em>p</em> = 0.67, respectively). In the MDD group, a linear relationship with age was observed for the HGF level (<em>p</em> = 0.03) but not the NG2 (<em>p</em> = 0.23) or Bcl-2 (<em>p</em> = 0.92) level. Trends toward significant positive linear relationships with age were observed for the levels of IL-1β (<em>p</em> = 0.06) and TNF-α (<em>p</em> = 0.08). Our data suggest that brain aging is advanced in individuals with MDD in part due to increased neuroinflammation and reduced pro-survival protein levels and myelination potential.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101107"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heritability of neonatal acute phase protein levels","authors":"Hugo Sjöqvist ,&nbsp;Martin Brynge ,&nbsp;Kristiina Tammimies ,&nbsp;Ralf Kuja-Halkola ,&nbsp;Sven Bölte ,&nbsp;Christina Dalman ,&nbsp;Renee M. Gardner ,&nbsp;Håkan Karlsson","doi":"10.1016/j.bbih.2025.101097","DOIUrl":"10.1016/j.bbih.2025.101097","url":null,"abstract":"<div><div>Levels of neonatal Acute Phase Proteins (APPs) have been associated with autism and schizophrenia. The relative contributions of genetic and environmental factors to variation in APP levels in the neonatal period are not known. Therefore, we used one of the largest twin samples to date to map the proportions of heritable and non-heritable factors to variations in APPs measured shortly after birth. Moreover, we investigated if any association existed between neonatal APP levels and autism, among monozygotic and dizygotic twins discordant for autism.</div><div>Twins were identified and enrolled from registers and a clinical twin study of autism in Sweden. The distributions of APPs measured in dried blood spots taken a few days after birth as part of a national screening program were standardized to reduce any analytical artifacts. The additive genetic (A), common (C) and unique (E) environment components were estimated, using the ACE model, on a sample of 92 twin pairs. We included 61 autism discordant twin pairs for estimating the association between the APPs and autism, using both non-fixed (between) and fixed (within) effects regression models.</div><div>For the ACE models, variations in α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, serum amyloid A and serum amyloid P were all largely explained by additive genetic factors (70–90 %). Variation in tissue plasminogen activator and procalcitonin were predominantly explained by common environmental factors (60–70 %) with a negligible contribution by genetic factors. Variations in levels of tissue plasminogen activator and procalcitonin in the neonatal period appear to be mainly explained by pregnancy and birth related factors. Variations in levels of other investigated acute phase proteins were largely explained by additive genetic factors. None of the APPs exhibited any significant association with autism in discordant mono- or dizygotic twin pairs. Our findings highlight the importance of considering potential familial confounding in future studies of association between any APP and autism.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101097"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of lifetime stressors and health behaviors with inflammation in young adults previously placed in youth residential care","authors":"David Bürgin ,&nbsp;Kristen Nishimi ,&nbsp;Vera Clemens ,&nbsp;Maria Meier ,&nbsp;Eva Unternaehrer ,&nbsp;Laura Gurri ,&nbsp;Evelyne Bruttin ,&nbsp;Nicolas Rohleder ,&nbsp;Paul Klauser ,&nbsp;Daniella Dwir ,&nbsp;Nimmy Varghese ,&nbsp;Anne Eckert ,&nbsp;Süheyla Seker ,&nbsp;Delfine d’Huart ,&nbsp;Cyril Boonmann ,&nbsp;Marc Schmid ,&nbsp;Aoife O'Donovan","doi":"10.1016/j.bbih.2025.101098","DOIUrl":"10.1016/j.bbih.2025.101098","url":null,"abstract":"<div><h3>Background</h3><div>Early life stressors (ELS) and stressful life events (SLEs) increase the risk for various physical health conditions, and health behaviors can modulate stress-associated risks. A key mechanism linking both lifetime stress and health behaviors with physical health outcomes is chronic low-grade inflammation. However, it is unclear how both stressor exposure and more proximal health behaviors are associated with inflammation in highly stress-exposed groups.</div></div><div><h3>Objectives</h3><div>Here, we investigated associations of lifetime stressors and health behaviors with peripheral inflammation in a highly stress exposed sample of young adults previously placed within youth residential care in Switzerland.</div></div><div><h3>Method</h3><div>We examined 126 young adults (<em>M</em>_Age = 26.3 years; 31 % female) who completed questionnaires to assess ELS, SLEs, and risky and protective health behaviors. Inflammatory markers (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10, and IL-1ra) were measured in venous blood using high sensitivity enzyme-linked immunosorbent assays (hsELISAs). Regressions estimated associations between ELS, SLEs, and health behaviors with each inflammatory marker.</div></div><div><h3>Results</h3><div>Our sample reported high levels of ELS and SLEs, as well as high levels of risky health behaviors. ELS and SLEs were mostly unassociated with young adult health behaviors, and both ELS and SLEs were not associated with inflammatory markers, adjusting for covariates. Regarding behavior, nicotine dependence was associated with higher pro-inflammatory markers and alcohol abuse marginally with a lower anti-inflammatory marker, while physical activity and better sleep quality were associated with lower pro-inflammatory markers, adjusting for covariates.</div></div><div><h3>Conclusions</h3><div>Among individuals with high levels of lifetime stress, cumulative ELS and SLEs were unassociated with inflammation, whereas risky behaviors were associated with higher, and protective behaviors with lower inflammatory markers. Interventions that reduce risky and promote protective health behaviors may lower inflammation and promote long-term health among individuals who have experienced high lifetime stressors exposure.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101098"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of endogenous IL-10 promotes resolution and tolerance of nitric oxide in microglia","authors":"Hsing-Chun Kuo ,&nbsp;Jia-Shing Chen ,&nbsp;Chun-Nun Chao ,&nbsp;Kam-Fai Lee ,&nbsp;Yi-Te Huang ,&nbsp;Pin-Cheng Mao ,&nbsp;Tzu-Chia Lin ,&nbsp;Shu-Chen Chiu ,&nbsp;Ya-Ling Huang ,&nbsp;Chun-Hsien Chu","doi":"10.1016/j.bbih.2025.101094","DOIUrl":"10.1016/j.bbih.2025.101094","url":null,"abstract":"<div><div>Endogenous interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is induced in a timely and coordinated manner to dampen microglia-mediated brain inflammation. However, it remains unclear how it alters the inflammatory process to shape the immune polarization of microglia. This study aimed to investigate the anti-inflammatory mechanisms of endogenous IL-10 in activated and tolerized microglia using in vitro multiple-reconstituted primary brain cell cultures and an in vivo IL-10 knockout (IL-10KO) animal model. Upon a single or repeated lipopolysaccharide (LPS) treatment regimen, the expression levels of the inflammatory factors during the neuroinflammatory/tolerance process were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and Griess reagent assay. ELISA data showed that cell-autonomous induction of endogenous IL-10 occurs in LPS-activated and LPS-tolerized microglia. Furthermore, comparing the LPS-elicited pro-inflammatory factor expressions at different neuroinflammatory stages between the wild-type and IL-10KO groups, our data revealed the failure of negative-feedback suppression of inducible nitric oxide synthesis (iNOS) during immune resolution in the IL-10KO brains. Moreover, LPS-treated IL-10KO microglia increase the supernatant level of nitrite and become overactive during late-stage inflammation, despite no changes in cell number; in contrast, LPS-tolerized IL-10KO microglia fail to program endotoxin tolerance of nitric oxide/inducible nitric oxide synthesis (iNOS). In summary, our data demonstrate that the cell-autonomous induction of endogenous IL-10 in microglia is crucial for mitigating brain immune responses, particularly in the resolution and tolerance of nitric oxide.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101094"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}