Figure 6.

Proposed mechanism of fatigue as a result of immunological dysfunction. Radiation-induced activation of the cytokine network results in a positive-feedback network of immune cells and cytokines. Increased levels of cytokines in the periphery result in activation of multiple immune cells including eosinophils. Activation of eosinophils further contributes to inflammation by producing more cytokines. Peripheral inflammation may result in abnormal muscle function leading to muscle fatigue. Cytokines may either directly enter the CNS or activate neuro-immune interactions resulting in decreased 5-HT production and abnormal NMDA receptor activity leading to central fatigue.