[Pathophysiology of fibroses. Progressive systemic scleroderma as a model disease]

Fibrosis is characterized by excessive deposition of connective tissue in the involved organs. Although the prime event in the pathogenesis is still poorly understood, several mechanisms are discussed, which finally result in the activation of fibroblasts. Recent studies have demonstrated that immunocompetent cells play a crucial role during the initial phases of the development of fibrosis. Therefore, several mediators have been characterized, which are secreted by platelets, lymphocytes and macrophages and which can attract fibroblasts, induce proliferation and collagen synthesis in mesenchymal cells. These include PDGF, EGF, TGF--beta and many others. In addition, gamma-interferon has been shown to inhibit chemotaxis of fibroblasts and to reduce collagen mRNA levels. A controlled interaction of all the different mediators is required to guarantee a normal functioning of connective tissue. Alterations in these regulation steps can result in excessive deposition of connective tissue and the development of fibrotic processes.