Inibição da TGF-beta 1 reduz a fibrose em músculos de camundongos com distrofia muscular mas aumenta a resposta inflamatória

Itália – a TGF-1 é uma citocina relacionada a fibrose; o seu bloqueio poderia auxliar no tratamento da distrofia muscular de Duchenne; neste estudo em camundongos o bloqueio da TGF-beta 1 com anticorpos causou uma melhora da alterações musculares o que foi um efeito positivo; no entanto eles observaram um aumento das células inflamatórias, o que poderia ser prejudicial e não era um efeito previsto e que não pode ser explicado. O resumo em inglês do artigo que será publicado em breve pode ser lido abaixo:

(IN PRESS: Journal of Neuroimmunology 2006) Immunomodulation of TGF-beta1 in mdx mouse inhibits connective tissue proliferation in diaphragm but increases inflammatory response: Implications for antifibrotic therapy

Francesca Andreetta, Pia Bernasconi, Fulvio Baggi, Paolo Ferro, Laura Oliva, Elisa Arnoldi, Ferdinando Cornelio, Renato Mantegazza, Paolo Confalonieri – Italy

Irreversible connective tissue proliferation in muscle is a pathological hallmark of Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease due to lack of the sarcolemmal protein dystrophin. Focal release of transforming growth factor-beta1 (TGF-h1) is involved in fibrosis development. Murine muscular dystrophy (mdx) is genetically homologous to DMD and histopathological alterations comparable to those in DMD muscles occur in diaphragm of older mdx mice. To investigate the early development of fibrosis and TGF-h1 involvement, we assessed diaphragms in 6–36-week-old mdx and C57/BL6 (control) mice for fibrosis, and used real-time PCR and ELISA to determine TGF-h1 expression. Significantly greater fibrosis and TGF-h1 expression were found in mdx from the 6th week. Mice treated with neutralizing antibody against TGF-h1 had lower levels of TGF-h1 protein, reduced fibrosis, unchanged muscles fiber degeneration/ regeneration, but increased inflammatory cells (CD4+lymphocytes). These data demonstrate early and progressive fibrosis in mdx diaphragm accompanied by TGF-h1 upregulation. Reduction of TGF-h1 appears promising as a therapeutic approach to muscle fibrosis, but further studies are required to evaluate long term effects of TGF-h1 immunomodulation on the immune system.

Fonte: http://www.distrofiamuscular.net/noticias.htm