SEARCH · Search PubMed

Results for “systemic inflammation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

605 recordsLinked to original sources

PubMed2026

Childhood Economic Mobility and Systemic Inflammation Among Men Who Experienced Low Income in Toddlerhood: The Moderating Role of Trait Hostility.

OBJECTIVE: Childhood economic upward mobility (ie, increases in family income across childhood) may attenuate links between childhood poverty and systemic inflammation in adulthood, the extent of which may vary depending on inter-individual differences in personality characteristics, including hostility. METHODS: Men who experienced low income in toddlerhood (N=171) were followed prospectively into adulthood. Annual family income was collected 12 times when men were 1.5 to 17 years old. Men completed the Cook-Medley Hostility Scale and had their fasting blood drawn to measure circulating levels of C-reactive protein (CRP) at age 32. Multiple linear regression analyses examined main and moderation effects of childhood economic upward mobility and adult hostility on CRP levels adjusting for income at 1.5 years, race, parent educational attainment, and adult income, education, waist circumference, and smoking status. RESULTS: Main effects were nonsignificant, but an interaction effect emerged. Counter to expectations, childhood economic upward mobility related to greater adult CRP as trait hostility decreased ( β =-0.203, P =.018). Simple slope analyses further revealed that childhood economic upward mobility was positively associated with CRP among men lower in hostility ( β =0.23, SE=0.09, P =.020) but was unrelated to CRP among men higher in hostility. Results of post hoc sensitivity analyses are also discussed. CONCLUSIONS: Counterintuitive findings suggest that for men who experience poverty in toddlerhood, the association between childhood economic upward mobility and adult CRP may be nuanced and even in the positive direction for men low in hostility, which aligns with work on unintended health consequences of upward mobility.

Humans↗

PubMed2026

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72 h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR = 5.12; 95% CI: 2.57-12.24; p < 0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity < 0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p = 0.045) and significantly improved risk reclassification (cNRI = 0.4778, p < 0.001; IDI = 0.0240, p = 0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗

PubMed2026

Glymphatic dysfunction mediates inflammation-driven vascular burden and cognitive decline in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is increasingly recognized as a disorder involving microvascular dysfunction, impaired perivascular clearance, and inflammatory processes. However, how systemic inflammatory burden, neurovascular coupling (NVC), glymphatic MRI markers, vascular lesion burden, and cognition are interrelated remains unclear. MATERIALS AND METHODS: In this prospective study, 155 patients with CSVD and 70 healthy controls (HCs) underwent multimodal MRI. NVC was quantified using the cerebral blood flow/fractional amplitude of low-frequency fluctuations ratio. Glymphatic function was assessed via the diffusion tensor image analysis along the perivascular space (ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) fractions. Structural equation modeling (SEM) was employed to evaluate the direct and indirect effects of inflammatory markers on vascular burden and cognitive performance. RESULTS: Patients with CSVD exhibited significantly diminished NVC (specifically in the right median cingulate and left frontal gyri) and impaired glymphatic function (lower ALPS-index; higher CPV and PVS fractions) compared to HCs. SEM revealed that inflammatory biomarkers exerted both a direct effect on vascular burden and a substantial indirect effect (accounting for 66.3% of the total effect) mediated through two pathways: a single-mediation path via glymphatic function (42.8%) and a serial-mediation path via NVC and glymphatic function (23.5%). Increased vascular burden was significantly associated with poorer cognitive performance. CONCLUSION: Inflammation drives CSVD progression and cognitive decline primarily through the disruption of NVC and glymphatic clearance mechanisms. These findings highlight glymphatic dysfunction as a critical mediator of inflammation-related structural brain damage.

Humans↗

PubMed2026

Comparison of the predictive performance of systemic immune-inflammation index and neutrophil-to-lymphocyte ratio for three-month poor functional outcome in ischemic stroke: a systematic review and meta-analysis.

INTRODUCTION: Ischemic stroke (IS) is a leading cause of global mortality and disability. Early and accurate prognosis is crucial for patient management. The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory biomarkers; however, their relative predictive value for three-month poor functional outcome (modified Rankin Scale [mRS] > 2) remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to 20 July 2025, adhering to PRISMA guidelines. Observational studies reporting the association of SII or NLR with three-month poor outcome were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Area under the curve (AUC), odds ratios (OR), and standardized mean differences (SMD) were pooled using random-effects models in Stata 16.0. RESULTS: Twenty-one studies involving 7520 IS patients were analysed. NLR demonstrated marginally superior discriminative ability compared to SII (AUC 0.71, 95% CI: 0.67-0.76 vs. 0.68, 95% CI: 0.64-0.71), though this difference was not statistically significant. Elevated NLR was significantly associated with poor outcome (OR = 1.26, 95% CI: 1.17-1.37, p < .001), whereas SII was not (OR = 1.00, 95% CI: 1.00-1.00, p = .384). Both markers showed moderate effect sizes (SMD: NLR = 0.69, SII = 0.72; p < .001). NLR performed better in non-intervention and Chinese subgroups, while SII exhibited consistent AUC values across treatment and ethnic subgroups. CONCLUSION: NLR and SII are accessible prognostic markers in IS. NLR demonstrates superior accuracy and a significant association with poor outcome, while SII shows greater stability across patient subgroups. Both may assist in risk stratification, in resource-limited settings.

Humans↗

PubMed2026

The Thyroid-Brain Network: Exploring Inflammation, Immune Mechanisms and Common Triggers in Thyroid-Related Neurological Dysfunction.

Autoimmune thyroid diseases (AITD), including Hashimoto's thyroiditis and Graves' disease, represent the most prevalent endocrine disorders worldwide, affecting hundreds of millions with profound but often under recognized neurological consequences. There are emerging lines of evidence establishing inflammation and immunity as the critical missing link connecting peripheral thyroid dysfunction to central nervous system manifestations. Thyroid hormones function as essential neuromodulators governing neurodevelopment, synaptic plasticity, and cognitive processing through integrated genomic and non-genomic mechanisms, with region-specific cerebral metabolic disturbances correlating with distinct neuropsychiatric symptoms. The immunological perspective reveals that AITD propagates neuroinflammation through convergent pathways: molecular mimicry enabling cross-reactivity between thyroid and neural antigens, cytokine-mediated disruption of neurotransmitter metabolism, HMGB1-driven glial activation, and blood-brain barrier compromise facilitating immune cell infiltration. The thyroid-gut-microbiota axis emerges as a critical mediator wherein dysbiosis perpetuates both thyroid autoimmunity and neuroinflammation through impaired serotonin precursor availability and increased intestinal permeability. Mitochondrial dysfunction represents an energetic common denominator, as thyroid hormone dysregulation directly impairs oxidative phosphorylation, producing region-specific cerebral metabolic disturbances. Simultaneous compromise of monoamine systems, cholinergic signaling abnormalities, and glutamate excitotoxicity creates a particularly toxic neurochemical state in untreated thyroid dysfunction. Common triggers such as psychological stress, gut dysbiosis, and mitochondrial impairment may activate interconnected pathways that simultaneously compromise thyroid and brain function, revealing that these disorders share fundamental mechanistic origins. These insights have been discussed in the current review to enhance the understanding of thyroid-brain function, the core mechanisms and consequences of functional deficits.

Journal Article↗

PubMed2026

Specialized pro-resolving mediators in obesity and overweight conditions: A systematic review of human and animal evidence on comparative differences and associations.

Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.

Animals↗

PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗

PubMed2026

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

In periods of sustained hyper-nutrition, pancreatic β-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that β-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of β-cell identity genes, particularly in a distinct subset of β-cells. These observations extend to humans, where the prevalence of an β-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of β-cell dysfunction that limits the compensatory capacity of β-cells, which is closely linked to the development of diabetes.

Animals↗

PubMed2025

Elucidation of the immunotoxicity of PEDOT: PSS on RAW264.7 macrophages by oxidative stress, inflammatory response, and NF-κB pathway activation.

Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) nanoparticles, widely used conductive polymers, pose environmental and health risks due to their nanoscale dispersion. However, the characteristics of PEDOT: PSS in aquatic systems and the underlying mechanisms of its toxicity in animal and cell models remain poorly understood. This study aimed to investigate the toxicological effects of PEDOT: PSS nanoparticles on macrophages, with a focus on RAW 264.7 cells. After an acute exposure to PEDOT: PSS nanoparticles at different concentrations (5, 10, 20 μg/mL), we observed significant impairments in cell viability, proliferation, migration, adhesion, and phagocytosis, as well as morphological alterations. Concurrently, there was a marked upregulation of inflammatory markers, including reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), indicating the induction of oxidative stress and inflammation. Mechanistically, PEDOT: PSS nanoparticles activated the nuclear factor kappa B (NF-κB) signaling pathway, a key regulator of inflammatory responses, suggesting that they may mediate inflammatory responses and cell damage via activation of the NF-κB signaling pathway. These findings reveal the toxic mechanism of PEDOT: PSS nanoparticles in macrophages and provide new insights into their biological safety implications.

Animals↗

PubMed2026

Association of galectin-3 in systemic lupus erythematosus: A systematic review and meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune condition showing persistent profiling of inflammation and damage of organs and immune system. Amongst many biomarkers for such autoimmune diseases, Galectin-3 (Gal-3) a β-galactoside-binding lectin responsible for regulation, inflammation, and fibrosis of immune repsonses, has engrossed researchers for further investigations as a potential biomarker. However, correlation has been studied between circulating Galectin-3 levels and SLE but outcomes still remain inconsistent. Therefore, this systematic review and meta-analysis evaluated the association between circulating galectin-3 levels and SLE.Materials and MethodsPubMed, Scopus, ScienceDirect, Web of Science, and Embase databases are extensively used for literature search. The last database search was conducted on September 6, 2025. Eligible studies included case control studies reporting circulating galectin-3 levels in individuals with SLE and healthy controls. Two independent reviewers performed study selection and data extraction. Study quality was evaluated using the Newcastle-Ottawa Scale. Comprehensive Meta-Analysis software was used for statistical analysis. Pooled effect sizes were calculated as mean differences with 95% confidence intervals. Heterogeneity was assessed using the Cochrane Q test and I2 statistics, and publication bias was evaluated using Begg's funnel plot and Egger's regression analysis.ResultsSeven eligible studies were included in the meta-analysis. The pooled results showed that patients with SLE had significantly higher circulating Galectin-3 levels than healthy controls (mean difference = 8.48; 95% CI: 3.84-13.12; p < 0.0001). Substantial heterogeneity was observed across studies (Tau square: 32.57, Q = 196.03; p < 0.0001, I2 = 96.93%). Sensitivity analysis confirmed the stability of the overall findings. Begg's funnel plot and Egger's regression analysis indicated no publication bias among studies. Subgroup analysis supports the results of the overall analysis.ConclusionThis meta-analysis depicts that galectin-3 may serve as a biomarker associated with SLE pathogenesis and inflammatory activity due to significantly elevated levels of circulating galectin-3 levels in patients with systemic lupus erythematosus.

Humans↗

PubMed2026

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans↗

PubMed2026

Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.

Anhedonia is a core feature of depression that reflects reward system dysfunction. Acute inflammatory challenge has been shown to induce transient anhedonia and reward processing deficits, but its effects on distinct components of social reward processes remain poorly understood. This randomized, double-blind, placebo-controlled study evaluated anhedonia and social reward responsivity following acute inflammatory challenge. Low-dose endotoxin (0.8 ng/kg body weight; n = 18) or placebo (same volume of 0.9% saline; n = 22) was administered to female adults (ages 25-44). Anhedonia (Snaith-Hamilton Pleasure Questionnaire) and blood samples for cytokine assessment were collected pre-infusion and 2 and 4 h post-infusion. Social reward motivation (wanting to engage in a social task) was assessed at a baseline eligibility visit and 2 h post-infusion. Sensitivity to positive social cues (attentional bias toward and recognition of happy faces) was assessed pre-infusion and 2 h post-infusion. Results showed that endotoxin increased anhedonic symptoms (p = .005) and decreased social motivation by 2 h post-infusion (p = .001); within the endotoxin condition, changes in both outcomes were associated with increases in TNF-α (p's < .04). A significant condition-by-time interaction for happy-face recognition (p = .011) was driven by increased accuracy in the placebo (p = .04) but not endotoxin (p = .43) condition. Endotoxin administration did not affect attentional bias toward happy faces. Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression. Future work could examine whether immune-related changes in social motivation contribute to motivational deficits in depression.

Humans↗

PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗

PubMed2026

Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.

Humans↗

PubMed2026

Effects of Acute Low- and Moderate-Dose Alcohol on Chronic Disease-Related Biomarkers in Healthy Light and Heavy Drinkers.

BACKGROUND: Alcohol consumption is a major contributor to global chronic disease, with growing evidence indicating health risks even at low levels of intake. However, mechanistic understanding of these risks relies heavily on preclinical models and observational data, leaving a critical gap in controlled experimental evidence regarding how alcohol perturbs human biological systems in vivo. METHODS: The present study utilized plasma samples from a randomized, placebo-controlled trial to evaluate the effects of low-dose (0.35 g/kg) and moderate-dose (0.60 g/kg) alcohol on disease-relevant biomarkers in 32 healthy adults (mean age = 25.0 ± 3.8 years; 21 female/11 male), characterized by light (n = 15) or heavy (n = 17) drinking. This design enabled evaluation of effects across dose, timescale, and drinking history, as well as assessment of their interactions. Plasma was collected at prebeverage baseline and hourly for 4 h afterward. Immunoassays quantified 10 disease-related biomarkers: adiponectin, angiogenin, D-dimer, high-sensitivity C-reactive protein (hsCRP), Intercellular Adhesion Molecule-1 (ICAM-1), Lipocalin-2 (LCN2), Matrix Metalloproteinase-7 (MMP-7), Matrix Metalloproteinase-9 (MMP-9), soluble Receptor for Advanced Glycation End-products (sRAGE), and Triggering Receptor Expressed on Myeloid cells 2 (TREM2). RESULTS: Main effects of group indicated that even in this young healthy sample, heavy drinking status was associated with higher levels of adiponectin, angiogenin, ICAM-1, LCN2, and sRAGE, a profile suggesting altered vascular and metabolic activity. Acute alcohol administration induced changes in sRAGE and hsCRP. Specifically, moderate-dose alcohol triggered an increase in the immunoglobulin sRAGE, which may reflect an acute compensatory response to inflammation and/or oxidative stress. Compared to placebo, hsCRP was lower in the low-dose alcohol condition; however, this finding should be interpreted in light of CRP biology. MMP-7, MMP-9, and LCN2 showed time-dependent fluctuations that were independent of experimental condition, highlighting the critical importance of placebo-controlled designs to account for diurnal/postprandial variation in immune biomarkers. CONCLUSION: Findings provide translational evidence that alcohol is associated with multisystem biomarker changes relevant to chronic disease and that alcohol-related biomarker perturbations vary by dose and chronicity.

Humans↗

PubMed2026

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

Humans↗

PubMed2026

Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N = 255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans↗

PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗