Chronic Occupational Stress and Immune–Inflammatory Dysregulation: Mechanisms, Clinical Consequences, Biomarkers and Implications for Occupational Medicine

Abstract

Chronic occupational stress is associated with adverse cardiovascular, metabolic, and mental-health outcomes, but the biological evidence linking workplace exposures to immune–inflammatory dysregulation varies in directness and clinical relevance. This narrative review distinguishes findings demonstrated directly in occupational populations from mechanisms extrapolated from general psychological-stress, experimental, and preclinical models, and evaluates the potential utility of candidate biomarkers in occupational health. Prospective occupational evidence supports a weak and heterogeneous association between adverse psychosocial working conditions and inflammatory activity, with the clearest signal reported for IL-6. Mechanistic studies implicate hypothalamic–pituitary–adrenal axis dysregulation, altered sympathetic signaling, reduced glucocorticoid sensitivity, NF-κB-related transcription, cytokine responses, immune-cell alterations, oxidative stress, and stress-responsive gene regulation; however, much of this evidence derives from non-occupational models and primarily supports biological plausibility. Occupational epidemiological evidence is strongest for cardiovascular and selected metabolic outcomes, while associations with depressive symptoms and psychological distress are recurrent but remain limited by concerns regarding causal inference. Evidence linking occupational stress specifically to autoimmune and skeletal outcomes remains comparatively indirect. C-reactive protein, IL-6, salivary cortisol, and hair cortisol remain research-oriented measures because none has demonstrated sufficient occupational-stress specificity, validated diagnostic accuracy, clinically actionable thresholds, or incremental predictive value beyond established psychosocial and clinical assessment. Routine biomarker-based diagnosis or surveillance is therefore not currently supported. Future research should prioritize repeated assessment of occupational exposures and biomarkers, temporally appropriate mediation analyses, independent replication, and external validation before biological monitoring can inform routine occupational-health practice.

The authors' abstract, as published at the source. Diagnostics, 2026 · DOI ↗