IMMUNOREGULATORY EFFECTS OF A SYNTHETIC MONOSACCHARIDE

Investigative attempts to identify novel therapy for inflammatory conn ective tissue diseases continue to evolve. Amiprilose hydrochloride (a miprilose HCl) is a synthetic carbohydrate shown to have anti-inflamma tory effects in animal models of inflammatory arthritis and in a multi center clinical trial. Interleukin-1 (IL-1) is an important mediator o f immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCl on IL-1 activity, production and receptor distribution were investigated. Drug effects o n IL-2 production and receptor distribution on lymphocytes were also e xplored. Potential regulation of IL-1 activity was determined by monit oring the effects of amiprilose HCl on IL-1 stimulated proliferation o f murine thymocytes and human synovial cells. inhibitory effects on IL -1 beta and IL-2 production by stimulated human peripheral blood monoc ytes were measured by ELISA and lymphocyte IL-1 beta and IL-2 receptor distribution were analyzed by flow cytometry. The results from in vit ro studies demonstrated that low concentrations of amiprilose HCl (1-1 00 mu g/ml) stimulated thymocyte proliferation and enhanced the prolif erative response of IL-1 stimulated human synovial fibroblasts. IL-1 b eta production in cultures of human peripheral blood monocytes was sig nificantly decreased after exposure of the cultures to varying doses o f amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decr eased IL-2 production at high concentrations of drug as compared to co ntrol. However, at doses of amiprilose HCl previously found to stimula te thymocyte proliferation (1-10 mu g/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1 beta or IL-2 receptor expression were observed. The r egulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.