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[Cancer Research 61, 884-888, February 1, 2001]
© 2001 American Association for Cancer Research


Advances in Brief

Interleukin-18 (IL-18) Synergizes with IL-2 to Enhance Cytotoxicity, Interferon-{gamma} Production, and Expansion of Natural Killer Cells1

Young-Ik Son, Ramsey M. Dallal, Robbie B. Mailliard2, Shinichi Egawa, Zdenka L. Jonak and Michael T. Lotze

Department of Surgery and Division of Biologic Therapeutics, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15261 [Y-I. S., R. M. D., R. B. M., S. E., M. T. L.], and Department of Oncology Research, SmithKline Beecham, King of Prussia, Pennsylvania 19406 [Z. L. J.]

We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-{gamma} production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-{alpha} expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.




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Copyright © 2001 by the American Association for Cancer Research.