CYTOKINES AND FIBROSIS

The aim of this paper is to review the role of cytokines in the physio pathology of fibrosis, with a particular emphasis to scleroderma (syst emic sclerosis), a localized or generalized connective tissue disease characterized by an increased collagen accumulation in skin and other main organs. Cytokine is the generic name for a group of (glyco)protei ns produced by nearly every cell in the body and able to regulate cell functions by paracrine or autocrine mechanisms. It includes interleuk ins, interferons, colony-stimulating factors, and polypeptide growth f actors. At the early stages of fibrotic process, connective tissue is invaded by inflammatory cells, mainly T-lyphocytes, mast cells and mon ocytes/macrophages. These cells are able to secrete a number of differ ent cytokines which will trigger a cascade of events leading to fibrob last activation and fibrosis. Some cytokines are able to induce fibrob last proliferation, some others to stimulate or to decrease collagen a nd other matrix macromolecule synthesis. Moreover, the effects of cyto kines are modulated by interactions with each other and with extracell ular matrix. Any alteration in this complex set of coordinated signals may result in uncontrolled collagen synthesis, leading to fibrosis.