Peripheral Levels of Selected Biomarkers in Patients with Post-Sarcoidosis Chronic Fatigue Syndrome

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Introduction: Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and multiple symptoms such as cognitive impairment and muscle pain, often linked to immune-inflammatory dysfunction. Sarcoidosis, a granulomatous disease with systemic inflammation, commonly causes fatigue, even during remission. This study examined whether fatigue and depressive symptoms in sarcoidosis remission relate to residual inflammation or oxidative stress. Recent studies highlight parallels between post-infectious fatigue syndromes, including Long COVID, and sarcoidosis-related fatigue, emphasizing IL-6 mediated pathways. Theoretical frameworks of immune–metabolic interactions further support the hypothesis that residual inflammation drives persistent fatigue in remission. Materials and methods: Seventy-one sarcoidosis patients were divided into three groups: remission with fatigue (RS/CFS, n=22), remission without fatigue (R/S, n=23), and active sarcoidosis (A/S, n=26). Fatigue was assessed with the Fatigue Assessment Scale (FAS), depressive symptoms with the Beck Depression Inventory (BDI), and quality of life with PHQ-9. Pulmonary function tests measured FEV 1 and FVC. Serum biomarkers (hsCRP, IL-6, TNF-α, total antioxidant status, and 8-isoprostanes) were measured by ELISA. Results: RS/CFS and A/S groups showed significantly higher fatigue, and depressive scores compared to R/S ( P < 0.05). HsCRP and IL-6 levels were elevated in fatigued patients (RS/CFS and A/S) versus non-fatigued (R/S) ( P < 0.05). IL-6 correlated moderately with fatigue and depression scores (r =0.33). No significant differences were found in TNF-α or oxidative stress markers. Pulmonary function was slightly reduced in fatigued patients and weakly correlated with mental fatigue (r = – 0.26). Conclusion: Our data support a role for low-grade systemic inflammation, especially elevated hsCRP and IL-6, in fatigue and depressive symptoms during sarcoidosis remission. Further research integrating inflammatory, oxidative, metabolic, and neuroendocrine pathways is needed to elucidate fatigue pathogenesis and develop targeted interventions. IL-6 may represent a potential biomarker of fatigue in sarcoidosis. These findings highlight the importance of persistent low-grade inflammation and may guide the development of future therapeutic strategies. Plain Language Summary: Fatigue is one of the most common and disabling symptoms in patients with sarcoidosis, even when the disease appears to be in remission. In this study, we compared three groups of patients with sarcoidosis – those in remission with fatigue, those with active disease, and those in remission without fatigue. We measured blood markers of inflammation and oxidative stress, as well as symptoms of fatigue and depression. We found that patients with fatigue had higher levels of inflammation, especially interleukin-6 (IL-6). This suggests that low-grade inflammation may play a role in persistent fatigue, and IL-6 might become a potential treatment target in the future. Keywords: sarcoidosis, chronic fatigue syndrome, inflammation, oxidative stress

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