Toll-like receptors on skeletal muscle

Th e term ‘idiopathic infl ammatory myopathy’ (IIM) usually refers to one of three related diseases: poly myositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each variation of the disease has defi ning characteristics (for example, the heliotrope rash of DM or the intramuscular rimmed vacuoles of IBM), but there are some common characteristics. In PM and DM, patients typically present clinically with diff use muscle weakness that is worse in proximal muscles than in distal muscles, whereas in IBM profound weakness may be present in both proximal and distal muscles. Histo logically, patients show muscle infl ammation, fi ber degeneration, and overexpression of the MHC class I molecule [1-3]. Th is muscle pathology is not always uniform, and many patients display isolated patches of infl ammation and degeneration in otherwise healthy muscle tissue. In aff ected patients, signifi cant causes of morbidity and mortality include diffi culty in performing daily activities, dysphagia, and respiratory failure [4,5]. Immunosuppressive therapies such as prednisolone and methotrexate are common fi rst-line treatments, with cyclosporine and other powerful immunosuppressants as second-line agents [6-8]. Unfortunately, these current therapies have produced mixed results; for example, patients with DM are most likely to benefi t from glucocorticoid therapy (with a reduction in infl ammation, and improvement in muscle function), and most PM patients typically respond to immunosuppressive therapy [9-11]. On the other hand, patients with IBM (and a subset of PM patients) do not typically respond to either glucocorticoids or other immunosuppressant therapies [7]. Studies have shown that the therapeutic response to glucocorticoid treatment varies signifi cantly; furthermore, the degrees of infl ammatory infi ltration and muscle function are dissociated, suggesting a role for other mechanisms in muscle dysfunc tion in these diseases [12,13]. Here we review some of the non-adaptive immune mechanisms that may be responsible for muscle weakness in the absence of overt infl ammation, and we provide evidence that skeletal muscle, but not infl ammation, is an active participant in the progression of muscle disease in these disorders.