Cortisol-CX3CL1 association and altered cytokine-chemokine profiles in emergency medical services personnel.
Frontiers in immunology · 2026-01-01 · Observational study
Abstract
BACKGROUND: Psychological distress may be associated with systemic immune regulation through neuroendocrine-immune pathways. Emergency medical services (EMS) personnel represent a high-demand occupational group, but their circulating cytokine and chemokine profiles and their relationship with psychological distress remain poorly characterized. This exploratory cross-sectional study examined inflammatory and physiological markers in EMS personnel compared with matched controls, with particular attention to the association between cortisol and CX3CL1 and exploratory sex-related patterns. METHODS: Seventy-eight participants, including 39 EMS personnel and 39 matched controls, underwent assessment of blood pressure, plasma cortisol, cytokines, chemokines, soluble adhesion molecules, and an exploratory panel of cardiovascular-related proteins. Psychological distress, including depression, anxiety, and stress symptoms, was assessed using the Depression, Anxiety and Stress Scale-21 in EMS personnel. Plasma concentrations of inflammatory mediators were analyzed after log10 transformation using two-way analysis of variance with group and sex as fixed factors. Spearman correlation analyses were used to explore associations between cortisol and inflammatory mediators. RESULTS: The EMS group showed higher systolic blood pressure and cortisol levels than the control group. The EMS group also exhibited a broad cytokine-chemokine alteration characterized by increased concentrations of several cytokines, including GM-CSF, IFN-α, IL-1α, IL-1β, IL-6, IL-10, and IL-13, and chemokines, including CCL2 and CX3CL1/fractalkine. In contrast, circulating E-selectin, P-selectin, and sICAM-1 were reduced in the EMS group. Most cytokines and chemokines formed a highly intercorrelated inflammatory cluster. However, CX3CL1 showed a more independent correlation pattern and was selectively associated with cortisol, whereas cortisol was not associated with the broader cytokine-chemokine network. This cortisol-CX3CL1 association was more evident among women. Within the EMS group, women reported higher anxiety and stress scores than men, whereas men showed higher systolic and diastolic blood pressure. CONCLUSION: EMS personnel exhibited an altered systemic cytokine-chemokine profile together with physiological changes and exploratory sex-related patterns. The selective association between cortisol and CX3CL1 suggests that circulating CX3CL1/fractalkine may reflect a stress-sensitive chemokine and a candidate marker of neuroendocrine-immune interaction. These findings support the relevance of integrating psychological, endocrine, and immune markers to characterize biological responses to psychological distress in high-demand healthcare populations.