The cytokine-chemokine patterns described in recent studies provide further evidence for predominance of Th1-mediated reactions in the different IIMs, inflammation-induced degenerative phenomena in inclusion body myositis, and a possible role for lymphoneogenesis in the sustained inflammatory response in dermatomyositis.

Our data suggest a possible beneficial role for CXCR1/2/4 ligands in managing muscle fiber damage control and tissue regeneration. Upregulation of endothelial chemokine receptors and CXCL8, CCL2, and CCL5 expression by cytotoxic macrophages may regulate myofiber necrosis.

Systemic manifestations of chronic obstructive pulmonary disease (COPD) include muscle wasting, and tumour necrosis factor alpha (TNFalpha) could represent a major inducer of these processes. We studied skeletal muscle histology in a murine model of cigarette smoke (CS)-induced COPD, comparing mice with different TNFalpha receptor genotypes. Muscles from hind limbs of wild type (WT), TNFalpha receptor 1 knockout (TNF alpha R1KO) and TNF alpha R2KO mice were prepared and weighed. The lower body weight, which was observed in CS-exposed WT and TNF alpha R1KO mice, was paralleled by reduced weights of gastrocnemius and biceps femoris muscle. The gastrocnemius muscle was evaluated for muscle fibre apoptosis and atrophy, and fibre-type distribution. CS-induced apoptosis was observed in all genotypes, while a significant reduction of cross-sectional areas of myofibres was present only in TNF alpha R2KO mice. A CS-induced fibre-type shift from the IIa to the IIb phenotype was observed in WT mice, an increase of muscle-fibre-type IIx was noticed in CS-exposed TNF alpha R2KO mice. Our data suggest that the skeletal muscle manifestations associated with this murine COPD model are under complex regulation by both TNFalpha receptors, but that TNF alpha R2 may be the most important determinant for the outcome of CS-induced myofibre apoptosis.

Idiopathic inflammatory myopathies 2.1. Dermatomyositis 2.2. Polymyositis 2.3. Sporadic inclusion body myositis 3. Chemokine levels in the idiopathic inflammatory myopathies 4. Localization of chemokines in the idiopathic inflammatory myopathies 4.1. Intramuscular blood vessels 4.2. Muscle fibers 4.3. Inflammatory cells 5. Perspectives for therapy: blocking chemokines as a novel approach 6. References