OKAMURA Haruki Institute for Advanced Medical Sciences, Department of Host Defence, Hyogo Colla, 医学部, 助教授 (60111043)
NAKANISHI Kenji Department of Immunology and Medical Zoology, Hyogo Collage of Medicine, Profess, 医学部, 教授 (60172350)
|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1998 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
We had analyzed protective roles of IL- 18, a novel cytokine which induced large amount of TEN-gammain synergies with IL-12, against Leishmania majar (L.major )infection, It was well known that, Th1 response dominant C57BL/6 mice showed resistanceto the L.major infection, while Th2 response dominant BALB/c mice were susceptible to the parasite infection. Recent studies reportedthatIL-18 plays an important role for induction and activation of Th1 helper T cells. Also we had established IL- 18 knockout mice to reveal the protective roles of IL- 18, in vivo.
We had revealed that, IL- 18 enhances the capability of IFN-gamma productions from NK and Th1 cells approximately ten-fold higher compare to stimulated cells with IL-12 alone. Further we had tested the protective effects of IL-18 and LL-12, onto L.major infected susceptible BALB/c mice. As the result, we had observed the induction of obvious protective effects against the infection. We had considered that, this protective effects were generated by successful induction of Th1 type helper T cells and productions of large amounts of IFN-gamma production from these Th1 cells. Further we had analyzed the alterations of the immune responses in C57BL/6 background IL- 18 knockout mice. Interestingly, these IL-18 knockout mice required longer elapse time to heal edema and ulcers caused by L.major infection, though C57BL/6 mice originally showed resistance to L.major infection. Moreover, we had observed that, serum levels of NO and IFN-gamma in L.major infected IL-18 knockout mice were relatively low compared to the wild type mice.
Taken these data together, we had concluded that, IL-18 plays important roles for the protective immunity to L.major infection, through inductions of Th1 type helper T cells and IFN-gamma production from these activated T cells. Our findings implicated possible therapeutic pathways using IL- 18 and IL-12 against L.major infection.