Impact of War-induced Stress on the Immune System: Mechanisms and Clinical Consequences

Background: Armed conflicts expose populations to physical, chemical, and psychosocial stressors that disrupt immune homeostasis through neuroendocrine dysregulation and inflammation. The recent US-Israel war against Iran in the Persian Gulf exemplifies this, with affected populations facing blast exposures, displacement, healthcare disruption, and chronic psychosocial stress. This narrative review aimed to synthesize evidence on molecular and clinical immune alterations induced by war-related stress.
Materials and Methods: This narrative review synthesized peer-reviewed literature using PubMed, Web of Science, and Google Scholar. We included original research, systematic reviews, and meta-analyses examining immune outcomes in conflict-exposed populations.
Results: War-related stress induces persistent immune dysregulation characterized by elevated pro-inflammatory mediators (interferon‑gamma, interleukin [IL]-2, tumor necrosis factor‑alpha, IL-6, C‑reactive protein), reduced anti-inflammatory cytokines, altered T-cell profiles, diminished natural killer (NK) cell numbers, and neuroinflammation with blood-brain barrier disruption. Post‑traumatic stress disorder involves dysregulated T-helper1 differentiation, altered chemokine expression, and downregulated suppressive microRNAs. Chronic stress drives hypothalamic‑pituitary‑adrenal axis activation, producing low-grade inflammation with glucocorticoid resistance. Accessible biomarkers including neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and C-reactive protein show promise for risk stratification. Sex-specific differences and transgenerational effects warrant further investigation.
Conclusion: War-induced immune dysfunction is multidimensional, affecting both military and civilian populations. Integrated biomarker monitoring, nutritional support, stress management, and targeted immunomodulatory therapies are priority interventions. Longitudinal studies and validated biomarkers across diverse populations are urgently required.