Infection and disease-induced neuroinflammation often manifest in non-neural symptoms, such as fatigue and muscle pain. However, the molecular pathways of these symptoms outside the CNS are poorly understood. Yang et al. found that CNS-derived IL-6 can directly regulate muscle physiology.

In mammals, retro-orbital injection of ORF3a increased CNS ROS production and activated the expression of cytokines, including IL-6.