Abstract
Background. Sporadic Inclusion body myositis (IBM) is an inflammatory disease that affects skeletal muscles in individuals over the age of 45. It leads to progressive muscle wasting and progressive disability and loss of independence for patients. Histologically, inflammation is characterised by myofibers displaying upregulated expression of major histocompatibility complex (MHC) class I molecules and invasion by immune cells comprising abundant CD8+ T cells. There is currently no cure, and regular exercise is the only recommended treatment recognised to be effective at limiting muscle inflammation and hindering the dis¬ease progression. In healthy men, physical exercise along with administration of testosterone was shown to increase skeletal muscle mass and performance in an additive fashion. Previous studies report that androgens are anti-inflammatory, inhibiting CD4+ T cell differentiation into inflammatory Th1 cells and promoting regulatory T cells. We hypothesised that combining testosterone supplementation with exercise training will reduce the level of autoimmune inflammation better than exercise alone, in men affected by IBM.
Methodology. We conducted a double-blind, placebo-controlled, cross-over randomised controlled trial (RCT) in fourteen men with IBM, to assess whether a period of exercise training using a personalised regime combined with topical application of testosterone, reduced the inflammatory immune response associated with this disease over and above just exercise alone. To assess the intervention efficacy, we analysed the phenotype of immune cells in the blood by flow cytometry, and measured the serum cytokine and chemokine content by Luminex immunoassay.
Results. The testosterone supplementation resulted only in a significant reduction of eosinophil numbers. However, we found additional immunoregulatory effects of the exercise training program over study that were testosterone-independent, including altered proportions of subsets within monocytes, T and B cells, and reduced circulating concentration of several pro-inflammatory cytokines such as IL-12, IL-17, TNF-alpha, MIP-1beta and sICAM-1.
Conclusions. Overall, our findings indicate that regular exercise training impacts the immune response in IBM and provides anti-inflammatory benefits to IBM patients; concomitant testosterone supplementation over a 12-week period provided essentially no anti-inflammatory effect over exercise alone. This work further emphasizes that maintaining a regular level of exercise helps in controlling inflammation in IBM, and also possibly, the pace of progression of the disease toward severe stages. We cannot exclude that incorporating testosterone supple-mentation to exercise training may provide a synergistic anti-inflammatory in IBM, but the optimal duration of intervention and the stage of disease progression when the intervention provides most benefits will need to be further characterised and refined to achieve optimal outcomes.