PT - JOURNAL ARTICLE AU - C Stevens AU - M Lipman AU - S Fabry AU - M Moscovitch-Lopatin AU - W Almawi AU - S Keresztes AU - M A Peppercorn AU - T B Strom TI - 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells. DP - 1995 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 399--406 VI - 272 IP - 1 4099 - http://jpet.aspetjournals.org/content/272/1/399.short 4100 - http://jpet.aspetjournals.org/content/272/1/399.full SO - J Pharmacol Exp Ther1995 Jan 01; 272 AB - The antiinflammatory agent sulfasalazine (SS) is prescribed to treat Crohn's disease, ulcerative colitis and rheumatoid arthritis. Activated T cells are present within diseased mucosal and synovial sites. We tested whether SS or its metabolites 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) inhibited the T-cell activation products interleukin 2 (IL-2) and interleukin 2 receptor alpha-chain (IL-2R alpha). Experiments were performed in phytohemaglutinin- and phorbol ester-stimulated peripheral blood mononuclear cells. Radioactive thymidine and leucine incorporation assayed DNA and protein synthesis, respectively. Enzyme-linked immunosorbent assay and Northern blot analysis measured IL-2 and IL-2R alpha. Lactate dehydrogenase release determined cell viability, and intracellular free calcium was measured by an indole fluorescent indicator. SS and 5-ASA, but not SP, inhibited T-cell proliferation and protein synthesis in phytohemaglutinin- and phorbol ester-stimulated peripheral blood monomuclear cells. 5-ASA (625 microM) markedly reduced culture supernatant IL-2 protein levels by 92% and steady-state IL-2 messenger RNA levels 4.4-fold at 24 and 18 hr, respectively. The supplementation of IL-2 restored T-cell proliferation only in 5-ASA-treated cultures. SS, 5-ASA and SP did not alter intracellular calcium accumulation after mitogenic stimulation. SS and 5-ASA (625 microM) caused 71% and 37% cytotoxicity, respectively, in 72-hr cultures. 5-ASA inhibits T-cell proliferation in part by blocking IL-2 messenger RNA accumulation and protein production downstream of the rise in cytosolic calcium. Inhibition of IL-2 production is an additional mechanism of action for 5-ASA.