Linomide, an immunomodulator that inhibits Th1 cytokine gene expression |
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Authors: | Arad, Gila Katzenellenbogen, Mark Levy, Revital Slavin, Shimon Kaempfer, Raymond |
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Affiliation: | Department of Molecular Virology, The Hebrew University-Hadassah Medical School Jerusalem 91120, Israel 1 Department of Bone Marrow Transplantation, Hadassah University Hospital Jerusalem 91120, Israel |
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Abstract: | Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulatingeffects in animal models, inhibiting toxic shock, progressiveautoimmune disease and cancer. In humans, linomide stronglyreduced the appearance of new lesions in multiple sclerosisyet enhanced immune responses after bone marrow transplantation.In contrast to these clear effects in vivo, attempts to showan effect of linomide in vitro have not been successful andits mode of action remains to be elucidated. Here we show thatat concentrations effective in vivo, linomide is active on humanperipheral blood mononuclear cells (PBMC), severely inhibitingthe induction by Staphylococcus aureus enterotoxin B of mRNAof three cytokine genes expressed in Th1 cells, those for IFN- ,IL-2, and tumor necrosis factor-ß. Yet, cell viabilitywas not affected by linomide. The extent of inhibition is dose-dependenton linomide. Linomide also blocked induction of IL-2 and IFN- mRNA by phytohemagglutinin. The inhibitory effect is expressedimmediately but can be enhanced significantly by a prolongedexposure of PBMC to linomide, reaching 10-fold. These resultssupport the concept that linomide antagonizes the activationof Th1 cells during a cellular immune response. |
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Keywords: | immunosuppression linomide superantigen Th1 cytokines |
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