Downregulation of TGF-β1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin

We used reverse(1) transcription-polymerase chain reaction to study the level of TGF-beta 1 mRNA expression and immunocytochemistry to examine the immunoreactive TGF-beta 1 in muscle biopsy specimens from five patients with dermatomyositis (DM) and five patients with inclusion body myositis (IBM) obtained before and after 3 months treatment with intravenous immunoglobulin (Mg). At baseline, the mRNA expression of TGF-beta 1 was increased up to fivefold in the muscles of DM patients compared to that of IBM patients. After IVIg, TGF-beta 1 was downregulated and the TGF-PI mRNA decreased twofold in the muscles of patients with DM who had successfully responded to therapy, but remained unchanged in the muscles of patients with IBM who did not respond. The downregulation of TGF-beta 1 in DM was associated with improvement of the muscle cytoarchitecture and reduction of the endomysial inflammation and connective tissue, suggesting that in DM the excess of TGF-beta 1 may be involved in the pathogenesis of chronic inflammation, fibrosis, and accumulation of extracellullar matrix proteins. (C) 2000 Academic Press.