Immunoregulatory Effects of a Synthetic Monosaccharide

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Abstract
Investigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve. Amiphlose hydrochloride (amiprilose HCl) is a synthetic carbohydrate shown to have anti-inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCI on IL-1 activity, production and receptor distribution were investigated. Drug effects on IL-2 production and receptor distribution on lymphocytes were also explored. Potential regulation of IL-1 activity was determined by monitoring the effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes and human synovial cells. Inhibitory effects on IL-1ß and IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1ß and IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCI (1-100 μg/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1ß production in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high concentrations of drug as compared to control. However, at doses of amiprilose HCI previously found to stimulate thymocyte proliferation (1-10 μg/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1ß or IL-2 receptor expression were observed. The regulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.

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