Interleukin-6: A potential link in the pathophysiology of restless legs syndrome

Iron deficiency, but also iron overload (as observed in Friedreich's ataxia), are associated with an increased prevalence of restless legs syndrome (RLS). The pathophysiological mechanisms linking these conditions to RLS remain unknown. Here, we propose that elevated circulating levels of interleukin-6 (IL-6) may represent a common underlying factor linking changes in iron homeostasis to the development of RLS. Peripheral IL-6 affects systemic iron distribution, central dopamine synthesis, and sensory neuron sensitivity, thereby contributing to the motor and sensory manifestations of RLS. We suggest that IL-6-mediated signaling may represent a potential therapeutic target for RLS.