Cachexia is characterized by progressive loss of body weight, muscle atrophy, fatigue, apathy and depression. Whereas inflammatory cytokines, in particular interleukin-6 (IL-6), are involved in the physical symptoms of cancer cachexia, the mechanisms behind the depressive symptoms are less understood. Now, Zhu, Starosta et al. identify an IL-6-sensing brainstem–basal ganglia circuit that orchestrates behavioural changes in cachexia.

The authors hypothesized that cytokines mediate the motivational deficits and identified IL-6 as one of the key cytokines that drives progression of precachectic to cachectic stages. IL-6 can penetrate the disrupted blood–brain barrier in cachectic mice, suggesting that peripheral IL-6 promotes cachexia. Indeed, reducing circulating IL-6 levels with monoclonal antibodies delayed cachexia onset.