title: Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12p40.
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-gamma 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-gamma 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-gamma 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-gamma 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.
authors.affiliation: Faculty of Medicine, First Department of Internal Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Kaori
authors.initials: K
authors.lastname: Uezu
authors.forename: Satomi
authors.initials: S
authors.lastname: Yara
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyagi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Koguchi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawase
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokota
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Yoshino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D021122:Protein Subunits; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma