Dual effects of caspase-1, interleukin-1β, tumour necrosis factor-α and nerve growth factor receptor in inflammatory myopathies

Objective To analyse the expression of factors potentially involved in skeletal muscle degeneration and regeneration in dermatomyositis (DM), systemic sclerosis (SSc), polymyositis (PM), systemic lupus erythematosus (SLE) and non-inflammatory myopathies. Methods Immunohistochemical staining of skeletal muscle biopsies (10 DM, 10 SSc, 10 PM, 10 SLE, 10 noninflammatory myopathies)for tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), activated caspase-1, pan-macrophage marker CD68, inducible nitric oxide synthase (NOS2) and nerve growth factor receptor (NGFR). TechMate(TM) staining robot and biotin-streptavidin protocol were used. Results Expression of TNF-alpha, IL-1beta, caspase-1 and NOS2 was found in the cytoplasm and sarcolemma of dystrophic skeletal muscle fibres. TNF-beta and IL-1beta immunoreactive profiles were faint and few and close to satellite nuclei-containing regenerating muscle fibres both in inflammatory and non-inflammatory myopathies. NGFR expression was found in comparable areas. In non-inflammatory inherited myopathies more nuclei were caspase-1 immunoreactive whereas caspase-1 expression was rarely seen in inflammatory myopathies, implying regeneration of the affected muscle fibres. Conclusion Prominent expression of the proinflammatory factors TNF-alpha, IL-1beta and NOS2 and caspase-1 is associated with muscle fibre damage, albeit when expressed to a low degree these factors may, like NGFR, contribute to muscle regeneration and heating.