Increased interleukin-17 production in patients with systemic sclerosis

Objective, To determine the role of a novel T cell-derived cytokine, interl eukin-17 (IL-17), which activates fibroblasts and endothelial cells, in the pathogenesis of systemic sclerosis (SSc), Methods. We examined IL-17 production by lymphocytes from the peripheral bl ood (PBL) and from fibrotic lesions of the skin and lungs of SSc patients b y reverse transcriptase-polymerase chain reaction and enzyme-linked immunos orbent assay. We also studied the effect of IL-17 on the proliferation of f ibroblasts and on the production of cytokines and the expression of adhesio n molecules on endothelial cells in vitro. Results, IL-17 messenger RNA was expressed in unstimulated PBL and lymphocy tes from the skin and lungs of SSc patients, but not in similar samples fro m patients with systemic Lupus erythematosus (SLE) or polymyositis/dermatom yositis or from healthy donors. IL-17 levels were also increased in the ser um of SSc patients, but not in that of SLE patients or healthy donors. IL-1 7 overproduction was significantly related to the early stage of SSc, but n ot to other clinical features of SSc, Moreover, IL-17 enhanced the prolifer ation of fibroblasts and induced the expression of adhesion molecules and I L-1 production in endothelial cells in vitro. Conclusion, IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients. These results sugge st that IL-17 overproduction plays an important role in the pathogenesis of SSc, especially in the early stages of the disease, by inducing the prolif eration of fibroblasts and the production of IL-1 and the expression of adh esion molecules on endothelial cells.