Cytokines as Potential Targets for Anti-Rheumatic Therapy: A Pharmacologist's View

The effects of anti-rheumatic drugs have been examined in vitro on lymphokine and monokine production and release from cultured human peripheral blood mononuclcar cells, and the action of monokine, IL-I on the release of PGE2 and collagenase from human synovial cells. Aspinn-like drugs are known to inhibit the vascular effects of prostaglandins (PGs) but they also enhanced lymphokine production because they prevent the PG-induced negative feedback effects Antimalanals inhibited monokine production in somewhat lower concentrations than PHA-induced lymphocyte proliferation. Gold compounds inhibit optimal PHA-induced 3H-TdR incorporation and monokine release, but only auranofin inhibited spontaneous monokine release Immunosuppresive agents, cyclosporin A, azathiopnne and 6-mercaptopunne, were less effective in inhibiting monokine production than lymphocyte proliferation indicating a specificity towards T lymphocytes. Glucocorticoids inhibit many cell functions, in particular T-cell function but at a different site from cyclosponn A. The inhibition of cytokine (monokincs and lymphokines) release might well provide a basis for a new experimental approach to the therapy of rheumatoid arthritis.