UP-REGULATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX AND INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION ON SCLERODERMA FIBROBLASTS AND ENDOTHELIAL-CELLS BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA IN THE EARLY DISEASE STAGE

Objective. To investigate the expression patterns of interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), both of which are potent inducers of class II major histocompatibility complex (MHC ) and intercellular adhesion molecule 1 (ICAM-1) expression, and their codistribution with HLA-DR and ICAM-1 in skin lesions, cultured fibro blasts, and peripheral blood mononuclear cells (PBMC) of systemic scle rosis (SSc) patients in different stages of disease. Methods. Investig ations were carried out using immunohistochemistry studies, reverse tr anscriptase-polymerase chain reaction, dot-blot hybridization, and cyt ometric analysis, Serum levels of TNF alpha were determined by enzyme- linked immunosorbent assay. Results. In the early inflammatory stage o f SSc, class II MHC and ICAM-1 expression could be detected on most en dothelial cells and on fibroblasts located especially in perivascular areas surrounded by infiltrating lymphocytes, which belong to the T he lper 1 phenotype expressing IFN gamma and TNF alpha, In this early dis ease stage, an enhanced expression of TNF alpha on cultured dermal fib roblasts and PBMC, as well as elevated serum titers of soluble TNF alp ha, could be found. Conclusion. These data suggest that class II MHC a ntigens and ICAM-1 on fibroblasts and endothelial cells are induced by IFN gamma and TNF alpha in an early stage of SSc after the influx of mononuclear cells, and may be important in the putative autoimmune res ponse and in the perpetuation of fibrotic processes in SSc.