Interleukin 18 (interferon gamma-inducing factor) exhibits antitumor effects in mice challenged intraperitoneally with syngeneic Meth A sarcoma (Meeting abstract).

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Interleukin 18 (interferon gamma-inducing factor) exhibits antitumor effects in mice challenged intraperitoneally with syngeneic Meth A sarcoma (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A2388 1997. Unique Identifier : AIDSLINE ICDB/98639388
Micallef MJ; Hanaya T; Kohno K; Arai S; Tanimoto T; Ikeda M; Kurimoto M; Fujisaki Institute, Hayashibara Biochemical Labs., Okayama 702,; Japan

Abstract: Interleukin 18 (IL-18, previously interferon gamma-inducing factor) is an 18.2 kD molecule produced by macrophages and related cells which reportedly enhances natural killer (NK) cell activity and T helper (Th) type 1 cytokine production in murine and human immunocompetent cell cultures. We here report that IL-18 exhibits significant (p less than 0.001) antitumor effects in vivo in mice challenged intraperitoneally (ip) with the syngeneic sarcoma, Meth A, especially when IL-18 was administered ip before (90% survival, n=10) or after (60% survival, n=10) tumor transplantation. The antitumor effects of pretreatment with IL-18 were abrogated by treatment with anti-asialo GM1 antibody ip, early after administration of IL-18, indicating the early participation of NK cells in the antitumor effects of IL-18. Mice pretreated with IL-18 which survived Meth A challenge resisted a second challenge with these cells but not challenge with Ehrlich carcinoma cells, indicating the induction of specific immune memory. The cytotoxic cells responsible for immune memory were present in the spleens of the resistant mice 80 days after challenge with Meth A and their activity could be inhibited by CD4+ cell depletion after treatment with antibody and complement. We conclude that treatment with IL-18 induces NK-mediated antitumor effects in Meth A-bearing mice followed by the generation of CD4-expressing cytotoxic T lymphocytes.

Keywords: Animal Antineoplastic Agents/*THERAPEUTIC USE Cytokines/*THERAPEUTIC USE Interferon Inducers/*THERAPEUTIC USE Killer Cells, Natural/IMMUNOLOGY Mice Sarcoma, Experimental/IMMUNOLOGY/*THERAPY Th1 Cells/IMMUNOLOGY ABSTRACT
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M9820752

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