Pathogenesis of Sporadic Inclusion Body Myositis: Significance of Inflammation and Implications for Therapeutic Strategies

Sporadic inclusion body myositis (sIBM) is the most common myopathy in older patients. An effective therapy is not available to halt the slowly progressive loss of ambulation. The complex pathology includes degenerative mechanisms with ail accumulation of aberrant molecules, most of all beta-amyloid. At the same time, a significant inflammation with an infiltration by cytotoxic T-cells occurs in the muscle. This review summarises recent work on different pathomechanisms of sIBM. It has been demonstrated that macro-autophagy is involved in the processing of beta-amyloid and related to antigen-presenting mechanisms. In view of the infiltration by cytotoxic T-cells, there is evidence of a relevant antigen presentation via so-called "non-classical" costimulatory molecules. Moreover, in sIBM there is a specific interrelationship between degeneration-associated molecules and inflammation in the muscle. In line with this, an accumulation of beta-amyloid can be induced by IL-1 beta in muscle cells. Taken together, these studies demonstrate that inflammatory mechanisms are of crucial relevance to the pathology of sIBM. Current therapeutic strategies include an antibody-mediated depletion of T-cells (alemtuzumab) and B-cells (rituximab). In the future, blockade of inflammatory molecules such as IL-1 beta and CXCL-9 as well as of beta-amyloid-associated mechanisms (BACE1, autophagy) should be taken into account.