In vitro immunomodulatory effects of sulfasalazine and its metabolites.

We assessed the in vitro effects of sulfasalazine and its 2 main metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) on functional aspects of peripheral blood lymphocytes (PBM) of normal controls and patients with rheumatoid arthritis (RA). Sulfasalazine, but not its 2 main metabolites, inhibited mitogen induced proliferative responses of PMB at high drug concentrations (100 micrograms/ml). Similar results were obtained with purified B lymphocytes. Sulfasalazine depressed, in a dose dependent manner, pokeweed mitogen induced Ig synthesis by PBM of normals and patients with RA. Moreover, synthesis of IgM rheumatoid factor was depressed to a greater degree than total IgM at low sulfasalazine concentrations (10-25 micrograms/ml). Both SP and 5-ASA were not inhibitory at the concentrations tested. Experiments with purified lymphocyte subpopulations indicated that sulfasalazine exerted its major inhibitory activity on the B lymphocyte. These studies indicate that sulfasalazine, but not its 2 main metabolites, has immunomodulatory characteristics which may be related to its therapeutic activity in RA.