The Dual Role of Myokines in Fatigue Associated with Inflammatory Joint Diseases

Fatigue is a prevalent and debilitating symptom in rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. Despite advances in reducing inflammation through treatments, fatigue often persists, underscoring its multifactorial etiology. A possible link between the persistent inflammation observed in rheumatic diseases and the onset of fatigue has been suggested. The discovery that skeletal muscles also secrete cytokines and myokines, has opened new avenues for research. This narrative review explores current mechanistic insights and evidence on the dural role of myokines in exacerbating or alleviating fatigue, particularly in the context of physical activity and chronic inflammation. Key myokines such as interleukin-6 (IL-6), myostatin, interleukin-15 (IL-15), brain-derived neurotrophic factor (BDNF), and irisin are examined for their influence on muscle-brain communication, neuroinflammation, and systemic metabolic processes. The findings highlight the potential of targeted myokine modulation as a therapeutic strategy for fatigue management.