EXPRESSION OF TNF-ALPHA BY HUMAN PLASMA-CELLS IN CHRONIC INFLAMMATION

Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory c ytokine and mediator of the inflammatory response, It has been implica ted in the pathogenesis of many inflammatory disorders, including rheu matoid arthritis (RA), septic shock, and Crohn's disease. Using a spec ific anti-human TNF-alpha antibody we detected immunoreactivity for th is cytokine in the cytoplasm of inflammatory cells in several chronic inflammatory disorders, including RA, scleritis, and polyarteritis nod osa, These cells were identified predominantly as IgG-expressing plasm a cells, Lymph nodes from patients with Hodgkin's lymphoma and breast cancer, but not from control subjects, were also found to contain TNF- alpha-positive plasma cells, Cultured EBV-B lymphocytes and a human pl asma cell line (ARH-77) when stimulated with phorbol myristate acetate demonstrated cytoplasmic TNF-alpha immunoreactivity, Western blot ana lysis of cell membranes and conditioned media from both cell types rev ealed the presence of the 26-kDa membrane-bound form and the 17-kDa so luble form of TNF-alpha, respectively, TNF-alpha was quantitated by en zyme-linked immunosorbent assay and found to be biologically active as determined by the L929 cytotoxicity assay, This is the first demonstr ation that plasma cells may be capable of modulating immune and inflam matory responses, not only by antibody production, but also by their s ecretion of a key inflammatory mediator, TNF-alpha.