Sulfasalazine inhibits the binding of TNF alpha to its receptor.

Sulfasalazine was found to exhibit a dose-dependent inhibition of human mucosal and peripheral blood cytotoxic T-cell function. The drug also inhibited the cytotoxic activity of supernatants from anti-CD3-triggered T-cells against murine L929 fibroblasts. TNF alpha has previously been shown to be primarily responsible for the lytic activity of such supernatants and this was confirmed. Sulfasalazine also inhibited the lytic activity of recombinant TNF alpha. When tested under conditions where TNF alpha was allowed to bind to but not lyse the target cells, the results suggested that the drug inhibits the action of this cytokine by inhibiting its binding to the cell membrane receptor. Additional evidence for an inhibitory effect of sulfasalazine on the membrane binding of TNF alpha was obtained by demonstrating a dose-dependent displacement of 125I-TNF alpha from HL60 cells. Although sulfasalazine is often considered to be a pro-drug for site-specific delivery of its component fragments 5-ASA and sulfapyridine, the results demonstrate an immunopharmacological property of the parent compound that is not shared with its component molecules.