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

Anticancer Res. Nov-Dec 1998;18(6A):4267-74.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antineoplastic Agents
  • CD40 Ligand
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Concanavalin A
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics*
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology
  • Interleukin-18 / pharmacology*
  • Interleukin-18 / therapeutic use
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Macrophage Activation / drug effects
  • Macrophage Activation / physiology*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Sarcoma, Experimental / immunology*
  • Sarcoma, Experimental / therapy
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Antibodies
  • Antineoplastic Agents
  • Interleukin-18
  • Membrane Glycoproteins
  • Concanavalin A
  • Interleukin-10
  • CD40 Ligand
  • Interleukin-12