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Methotrexate inhibits macrophage activation as well as vascular and cellular inflammatory events in rat adjuvant
W J Johnson1, M J DiMartino, P C Meunier
1Department of Immunology, Smith Kline and French Laboratories, King of Prussia, PA 19406.
Abstract:
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.
Insights
Methotrexate effectively treats arthritis by reducing swelling and inhibiting macrophage activation, unlike indomethacin or prednisolone. This study highlights methotrexate
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Macrophage activation is linked to the development and progression of arthritic lesions.
- Previous studies established an association between macrophage activation variables and adjuvant-induced arthritis.
Purpose of the Study:
- To investigate how antiarthritic agents modulate macrophage activation variables.
- To compare the effects of indomethacin, prednisolone, and methotrexate on both macrophage activation and arthritic lesions.
Main Methods:
- Assessing hindpaw edema as a measure of inflammation.
- Measuring macrophage activation markers, including Ia expression, prostaglandin E2 (PGE2), and interleukin-1 (IL-1) production.
- Evaluating the influx of Ia-positive macrophages into synovial tissue.
Main Results:
- Indomethacin reduced hindpaw edema but did not affect macrophage activation markers.
- Prednisolone inhibited hindpaw edema and IL-1 production.
- Methotrexate demonstrated efficacy in reducing hindpaw edema and inhibiting all assessed macrophage activation variables (PGE2, IL-1, cyanine dye accumulation) and macrophage infiltration into synovial tissue.
Conclusions:
- Methotrexate is superior to indomethacin and prednisolone in modulating macrophage activation pathways relevant to arthritis.
- Targeting macrophage activation alongside inflammation is crucial for effective antiarthritic therapy.
- Methotrexate's comprehensive effects suggest it as a key therapeutic agent for managing adjuvant-induced arthritis.