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Effects of methotrexate, sulphasalazine and aurothiomalate on polymorphonuclear leucocytes in rheumatoid arthritis
M Storgaard1, M P Jensen, K Stengaard-Pedersen
1Department of Medicine and Infectious Diseases, Marselisborg Hospital, Denmark.
Abstract:
The aim of the study was to evaluate the effects of treatment with methotrexate, sulphasalazine and aurothiomalate on polymorphonuclear leucocytes (PMN) in rheumatoid arthritis (RA). Circulating PMNs from 58 RA patients treated with either methotrexate (n = 27), sulphasalazine (n = 16) or aurothiomalate (n = 15) were assayed for their chemotactic capacity and generation of superoxide anions. The expression of CD18/CD11b was measured for 17 RA patients treated with methotrexate. Chemotaxis and generation of superoxide anions were not affected by any of the three drugs. We found no difference in the expression of CD18/CD11b in RA patients treated with methotrexate compared to healthy subjects. Further methotrexate and aurothiomalate did not in vitro alter chemotaxis, generation of superoxide anion or expression of CD18/CD11b on normal PMNs. In conclusion we found no evidence that the effect of methotrexate, aurothiomalate or sulphasalazine in RA can be explained by modulation of chemotactic ability or superoxide anion generation of peripheral circulating PMNs.
Insights
Methotrexate, sulphasalazine, and aurothiomalate treatments did not alter polymorphonuclear leucocyte (PMN) function in rheumatoid arthritis (RA) patients. These drugs do not impact PMN chemotaxis or superoxide anion generation, suggesting other mechanisms are involved in RA treatment.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
- Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulphasalazine, and aurothiomalate are used to manage RA.
- The precise mechanisms by which these DMARDs exert their therapeutic effects, particularly on immune cell function, require further elucidation.
Purpose of the Study:
- To investigate the impact of methotrexate, sulphasalazine, and aurothiomalate on the function of polymorphonuclear leucocytes (PMNs) in patients with rheumatoid arthritis (RA).
- To assess whether these commonly used RA medications modulate PMN chemotaxis, superoxide anion generation, and CD18/CD11b expression.
Main Methods:
- Analysis of circulating PMNs from 58 RA patients undergoing treatment with methotrexate, sulphasalazine, or aurothiomalate.
- Assays conducted included measurement of PMN chemotactic capacity and superoxide anion generation.
- Expression of CD18/CD11b was evaluated in a subset of methotrexate-treated patients and compared to healthy controls.
- In vitro experiments assessed the direct effects of methotrexate and aurothiomalate on normal PMN function.
Main Results:
- No significant alterations in chemotaxis or superoxide anion generation were observed in PMNs from RA patients treated with any of the three drugs.
- No difference in CD18/CD11b expression was found between RA patients on methotrexate and healthy subjects.
- In vitro studies demonstrated that methotrexate and aurothiomalate did not affect the functional parameters or cell surface marker expression of normal PMNs.
Conclusions:
- The study found no evidence that the therapeutic effects of methotrexate, sulphasalazine, or aurothiomalate in RA are mediated through the modulation of peripheral circulating PMN chemotactic ability or superoxide anion generation.
- These findings suggest that the mechanisms of action for these DMARDs in RA likely involve other immune pathways or cell types.
- Further research is warranted to fully understand the immunomodulatory effects of these important RA therapies.