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.
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000378:metabolism; D019804:Mesalamine; D012217:Rheumatoid Factor / Q000096:biosynthesis; D013424:Sulfanilamides / Q000494:pharmacology*; D013427:Sulfapyridine / Q000494:pharmacology*; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D007075:Immunoglobulin M; D007136:Immunoglobulins; D013424:Sulfanilamides; D012460:Sulfasalazine; D019804:Mesalamine; D012217:Rheumatoid Factor; D013427:Sulfapyridine