Immunoregulatory Effects of a Synthetic Monosaccharide
作者:
ChangD. M.,
期刊:
Immunopharmacology and Immunotoxicology
(Taylor Available online 1995)
卷期:
Volume 17,
issue 3
页码: 437-450
ISSN:0892-3973
年代: 1995
DOI:10.3109/08923979509016380
出版商: Taylor&Francis
数据来源: Taylor
摘要:
AbstractInvestigative 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-1ßand IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1ßand IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCI (1-100μg/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1ßproduction 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 (1-10μg/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1ßor 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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