Methotrexate in rheumatoid arthritis: studies with animal models.
The present studies have shown that low doses of methotrexate can suppress the inflammation and joint destruction associated with animal models of arthritis. The antiinflammatory effects of methotrexate are probably related to its inhibitory effect on chemotaxis. At the low doses used, methotrexate does not induce systemic immunosuppression. In methotrexate-treated rats, an improvement in IL-2 synthesis is observed and increases in IL-2 levels are expected to improve cell mediated immunity. Suppressor cells appear to be very sensitive to methotrexate. Macrophage function is modulated by methotrexate. All of these effects including the effects on joint destruction are probably due to inhibition of DHFR activity of critical cells that are involved in the pathogenesis of rat arthritis induced either by adjuvant or by streptococcal cell walls. Some of these effects have been extended to human arthritis but additional studies are required to understand how low dose methotrexate exerts its beneficial effects in humans.
Kerwar
S S
SS
Department of Inflammation and Immunology, American Cyanamid Company, Pearl River, New York 10965.
Oronsky
A L
AL
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D008727:Methotrexate / Q000378:metabolism / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D008727:Methotrexate