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  • Title: Augmentation of in vitro interleukin 10 production after in vivo administration of interleukin 18 is activated macrophage-dependent and is probably not involved in the antitumor effects of interleukin 18.
    Author: Micallef MJ, Tanimoto T, Kohno K, Ikeda M, Ikegami H, Kurimoto M.
    Journal: Anticancer Res; 1998; 18(6A):4267-74. PubMed ID: 9891477.
    Abstract:
    We have previously shown that interleukin (IL)-18 protects mice from intraperitoneal transplantation with syngeneic Meth A sarcoma, and in the process induces the production of large amounts of IL-10 from mitogen-stimulated treated mouse spleen cells, with a simultaneous augmentation of natural killer (NK) cell activity. Using in vivo and in vitro cell depletion methods, we now show that the cells producing IL-10 are neither NK cells nor macrophages (M phi), but that the IL-10 production is dependent on the presence of treated mouse M phi. Anti-IL-12 and anti-CD40L neutralizing antibodies could not inhibit the production of IL-10. Although IL-18-treated normal mouse enriched T cells stimulated with anti-CD3 and anti-CD28 antibodies failed to produce IL-10, the cytokine was also undetectable in culture supernatants of IL-18-treated nude mouse spleen cells, indicating that T cells were directly involved in the induced production of IL-10. Flow cytometry for intracellular IL-10 confirmed that CD8+ T cells and other, as yet unidentified spleen cell sub-sets were secreting IL-10, but only a small percentage of CD4+ cells produced IL-10. In vivo experiments using anti-IL-10 antibody indicated that IL-10 may not be directly involved in the antitumor effects of IL-18.
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