HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Osaki, T. Articles by Tahara, H. Search for Related Content PubMed PubMed Citation Articles by Osaki, T. Articles by Tahara, H.

IFN--Inducing Factor/IL-18 Administration Mediates IFN-- and IL-12-Independent Antitumor Effects¹

Tadashi Osaki^*, Jean-Marie Péron^*, Quan Cai^*, Haruki Okamura, Paul D. Robbins, Masashi Kurimoto^§, Michael T. Lotze^*, and Hideaki Tahara^2,*,

Departments of ^* Surgery and Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; Division of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo; and ^§ Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan

We evaluated the mechanism of the antitumor effects of mouse rIFN--inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN- levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN- or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8⁺ T cells, but not CD4⁺ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4⁺ T cells and NK cells, but in IFN-- and IL-12-independent pathways.