Methotrexate inhibits macrophage activation as well as vascular and cellular inflammatory events in rat adjuvant induced arthritis.
We demonstrated previously that variables of macrophage activation are associated with the development and progression of the arthritic lesion in the model of adjuvant induced arthritis. This association was investigated further by assessing the ability of antiarthritic agents to modulate variables of macrophage activation in direct comparison to effects on the arthritic lesion. Whereas indomethacin effectively reduced hindpaw edema, it had no significant effect on Ia expression or on any measurement of activation. Prednisolone inhibited hindpaw edema and the production of interleukin-1 (IL-1) by splenic macrophages. Only methotrexate inhibited hindpaw edema and all variables of macrophage activation (PGE2 and IL-1 production, cyanine dye accumulation) as well as the influx of Ia positive macrophages into synovial tissue.
Johnson
W J
WJ
Department of Immunology, Smith Kline and French Laboratories, King of Prussia, PA 19406.
DiMartino
M J
MJ
Meunier
P C
PC
Muirhead
K A
KA
Hanna
N
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000473:pathology*; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D002232:Carbocyanines; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000276:immunology / Q000517:prevention & control; D005456:Fluorescent Dyes; D005528:Foot; D006614:Hindlimb; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007375:Interleukin-1; D007376:Interleukin-2; C018528:3,3'-dipentyl-2,2'-oxacarbocyanine; D015232:Dinoprostone; D008727:Methotrexate