Interleukin-6: A neuro-active cytokine contributing to cognitive impairment in Duchenne muscular dystrophy?

•Dystrophin loss in Duchenne Muscular Dystrophy (DMD) results in cognitive deficits.•Circulating interleukin-6 is chronically elevated in individuals with DMD.•Interleukin-6 may contribute to DMD-associated cognitive dysfunction. Interleukin-6 (IL-6) is a pro-inflammatory cytokine, classically associated with orchestrating an immune response to invading pathogens. However, IL-6 can also directly or indirectly modify central nervous system function, and thereby alter higher-order functions, such as learning and the consolidation of memories. IL-6 is chronically elevated in Duchenne Muscular Dystrophy (DMD), a neuromuscular disorder arising when a mutation causes the loss of the structural protein, dystrophin. Absence of dystrophin leads to progressive immobility, chronic inflammation and premature death. However, the role of dystrophin as a mechano-transducing signalling molecule is unnecessary in non-contracting cells such as neurons, where it may play a role in synapse formation. Specific brain regions, including the hippocampus, which is the site of memory acquisition, expresses dystrophin and therefore, loss of this protein may underlie variable deficits in cognitive function that are common in individuals with DMD. This review will evaluate the potential role of IL-6 in cognitive dysfunction in dystrophin-deficient DMD.