Abstract
OBJECTIVE: To further elucidate the immunomodulating effects of anti-tumour necrosis factor alpha treatment in rheumatoid arthritis (RA) by studying changes in plasma levels of transforming growth factor beta (TGFbeta) in patients with RA undergoing etanercept treatment. METHODS: Plasma levels of TGFbeta1 and TGFbeta2 were determined in 26 patients with RA during six months of etanercept treatment and compared with disease activity and laboratory parameters, including matrix metalloproteinase-3 (MMP-3) and interleukin 6 (IL6). RESULTS: Before treatment all patients had raised TGFbeta1, IL6, and MMP-3 levels. In the course of treatment IL6 and MMP-3 levels decreased significantly, accompanied by a drop in serological markers (C reactive protein and erythrocyte sedimentation rate) and clinical disease activity (visual analogue scale and Thompson joint score). By contrast, high levels of latent TGFbeta1 were present in all specimens over the entire six months. TGFbeta2 levels did not change during treatment. CONCLUSION: Etanercept treatment induces subtle changes in the cytokine network. Although the proinflammatory cytokine IL6 is down regulated, the persistence of high TGFbeta plasma levels indicates the existence of as yet unknown mechanisms for TGFbeta overexpression in RA. This may predispose to severe infections and can cause an altered tumour defence.