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  • Title: Linomide, an immunomodulator that inhibits Th1 cytokine gene expression.
    Author: Arad G, Katzenellenbogen M, Levy R, Slavin S, Kaempfer R.
    Journal: Int Immunol; 1996 Oct; 8(10):1603-7. PubMed ID: 8921440.
    Abstract:
    Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulating effects in animal models, inhibiting toxic shock, progressive autoimmune disease and cancer. In humans, linomide strongly reduced the appearance of new lesions in multiple sclerosis yet enhanced immune responses after bone marrow transplantation. In contrast to these clear effects in vivo, attempts to show an effect of linomide in vitro have not been successful and its mode of action remains to be elucidated. Here we show that at concentrations effective in vivo, linomide is active on human peripheral blood mononuclear cells (PBMC), severely inhibiting the induction by Staphylococcus aureus enterotoxin B of mRNA of three cytokine genes expressed in Th1 cells, those for IFN-gamma, IL-2, and tumor necrosis factor-beta. Yet, cell viability was not affected by linomide. The extent of inhibition is dose-dependent on linomide. Linomide also blocked induction of IL-2 and IFN-gamma mRNA by phytohemagglutinin. The inhibitory effect is expressed immediately but can be enhanced significantly by a prolonged exposure of PBMC to linomide, reaching 10-fold. These results support the concept that linomide antagonizes the activation of Th1 cells during a cellular immune response.
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