Immunological abnormalities in rats with adjuvant-induced arthritis--II. Effect of antiarthritic therapy on immune function in relation to disease development.
The effects of the experimental immunomodulatory agent tilomisole (Wy-18,251; (3-(p-chlorophenyl) thiazolo [3,2-a]benzimidazole-2-acetic acid) on disease development and immune function in rats with adjuvant-induced arthritis was assessed in comparison with indomethacin and levamisole. Daily p.o. administration of tilomisole (100-200 mg/kg/day) to M. butyricum-injected rats significantly reduced both edema and bone erosion in the uninjected paw. Moreover, tilomisole treatment restored to normal the diminished Con A-induced proliferative response and IL 2 synthesis observed in spleen cells from arthritic rats, but had no effect on macrophage IL 1 production. In contrast, levamisole treatment (25 mg/kg/day) of arthritic rats improved splenic immune function but did not influence paw edema or bone erosion. Conversely, indomethacin (1 mg/kg/day) significantly reduced paw edema and bone erosion but did not improve the deficient proliferative response or IL 2 synthesis by "arthritic" spleen cells. These results indicate that tilomisole possesses combined antiinflammatory and immunomodulatory activity in adjuvant-arthritic rats which is distinctly different from the effects of either indomethacin or levamisole. Moreover, these data suggest that tilomisole has potential disease-modifying activity in arthritis, which is currently being more closely examined in clinical trials.
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002478:Cells, Cultured; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007978:Levamisole / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011919:Rats, Inbred Strains
D001562:Benzimidazoles; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007978:Levamisole; C029171:tilomisole; D007213:Indomethacin