Chronic Fatigue Syndrome (CFS) is a debilitating disorder with no clear etiology. Many, but not all, patients with CFS evidence signs of neuroimmune dysfunction prompting the suggestion that there exist subgroups of CFS patients with significant neuroimmune dysfunction while other subgroups of diagnosed patients may suffer from CFS-like symptoms due to other causes. Research has demonstrated that emotional distress responses impact CFS symptoms and that having adequate coping skills may predict less illness severity among individuals with CFS. However, no study to date has examined the influence of a comprehensive set of stress management skills on CFS symptoms nor has prior work evaluated if a relationship between stress management skills and CFS symptoms is mediated by lowered levels of emotional distress. Given the breadth of research literature linking neuroimmune dysfunction to emotional distress symptoms such as depression, and to physical symptoms such as fatigue, this study sought to examine a mediation model in which perceived stress management skills predict physical symptoms via lowered emotional distress. Moreover this study also sought to examine whether this model is most salient in individuals with a higher degree of neuroimmune dysfunction. In total, 117 individuals with CFS provided blood and saliva samples, as well as self-report measures of emotional distress, perceived stress management skills (PSMS), and CFS symptoms including fatigue. Plasma interleukin-2 (IL-2), IL-5, IL-6, IL-12, and tumor necrosis factor-alpha (TNF-a) and diurnal salivary cortisol were analyzed. This study examined relations among perceived stress management skills, emotional distress, and physical symptoms in CFS patients who did and did not evidence neuroimmune abnormalities. Results indicated that higher levels of perceived stress management skills were related to lower levels of emotional distress, which related to lower levels of fatigue and a lower total symptom severity score. Greater levels of PSMS were also associated with lower circulating levels of IL-2 and a more negative diurnal cortisol slope. The indirect relationship between perceived stress management skills and fatigue via emotional distress was moderated by level of plasma IL-6, such that it was significant in participants with elevated levels of IL-6, but not significant in those participants with lower levels of IL-6. No other neuroendocrine or cytokine indicator functioned as a moderator of this relationship. In conclusion, the relationship between perceived stress management skills and fatigue via emotional distress was more pronounced in individuals with greater levels of the circulating pro-inflammatory cytokine IL-6. These findings support the need for research examining the impact of stress management interventions in subgroups of CFS patients showing neuroimmune dysfunction
