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Infection and Immunity, May 1999, p. 2585-2589, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Interleukin-18 (IL-18) in Mycobacterial Infection in IL-18-Gene-Disrupted Mice

Isamu Sugawara,1,* Hiroyuki Yamada,1 Hirotaka Kaneko,1 Satoru Mizuno,1 Kiyoshi Takeda,2 and Shizuo Akira2

Department of Molecular Pathology, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo 204-0022,1 and Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Hyogo 663,2 Japan

Received 23 December 1998/Returned for modification 19 January 1999/Accepted 1 March 1999

Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma ), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha ), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma , and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression.

* Corresponding author. Mailing address: Department of Molecular Pathology, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan. Phone: 81 424 92 5075. Fax: 81 424 92 4600. E-mail: sugawara{at}jata.or.jp.

Infection and Immunity, May 1999, p. 2585-2589, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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