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Analysis of the effects of cyclosporine A (25–28 mgkg −1 ) and/or methotrexate (0.1 mgkg −1 ) treatments on dipeptidyl peptidase IV (DPPIV) and prolyl oligopeptidase (POP) activities and on algesic response in two distinct status of murine macrophages (M φ s) was undertaken. In resident M φ s, DPPIV and POP were affected by neither individual nor combined treatments. In thioglycolate-elicited M φ s, methotrexate increased DPPIV (99–110%) and POP (60%), while cyclosporine inhibited POP (21%). Combined treatment with both drugs promoted a rise (51–84%) of both enzyme activities. Only cyclosporine decreased (42%) the tolerance to algesic stimulus. Methotrexate was revealed to exert prevalent action over that of cyclosporine on proinflammatory M φ  POP. The opposite effects of methotrexate and cyclosporine on POP activity might influence the availability of the nociceptive mediators bradykinin and substance P in proinflammatory M φ s. The exacerbated response to thermally induced algesia observed in cyclosporine-treated animals could be related to upregulation of those mediators.

Methotrexate and Cyclosporine Treatments Modify the Activities of Dipeptidyl Peptidase IV and Prolyl Oligopeptidase in Murine Macrophages