Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: A comparative study with IL-12p40

Yuki Kinjo, Kazuyoshi Kawakami, Kaori Uezu, Satomi Yara, Kazuya Miyagi, Yoshinobu Koguchi, Tomoaki Hoshino, Masaki Okamoto, Yusuke Kawase, Koichi Yokota, Kohichiro Yoshino, Kiyoshi Takeda, Shizuo Akira, Atsushi Saito

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

The present study was conducted to critically determine the protective role of IL-18 in host response to Mycobacterium tuberculosis infection. IL-18-deficient (knockout (KO)) mice were slightly more prone to this infection than wild-type (WT) mice. Sensitivity of IL-12p40KO mice was lower than that of IL-12p40/IL-18 double KO mice. IFN-γ production caused by the infection was significantly attenuated in IL-18KO mice compared with WT mice, as indicated by reduction in the levels of this cytokine in sera, spleen, lung, and liver, and its synthesis by spleen cells restimulated with purified protein derivatives. Serum IL-12p40 level postinfection and its production by peritoneal exudate cells stimulated with live bacilli were also significantly lower in IL-18KO mice than WT mice, suggesting that attenuated production of IFN-γ was secondary to reduction of IL-12 synthesis. However, this was not likely the case, because administration of excess IL-12 did not restore the reduced IFN-γ production in IL-18KO mice. In further studies, IL-18 transgenic mice were more resistant to the infection than control littermate mice, and serum IFN-γ level and its production by restimulated spleen cells were increased in the former mice. Taken together, our results indicate that IL-18 plays an important role in Th1 response and host defense against M. tuberculosis infection although the contribution was not as profound as that of IL-12p40.

Original languageEnglish
Pages (from-to)323-329
Number of pages7
JournalJournal of Immunology
Volume169
Issue number1
DOIs
Publication statusPublished - 2002 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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