THE PROTECTIVE ROLE OF IL-12 AND IL-18 IN MOUSE VIRAL MYOCARDITIS

Liu YL, Hu XH, Cheng LM, Dong JH, et al.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Objectives: To study the role of IL-12 and IL-18 in the pathogenesis of mouse viral myocarditis, recombined IL-12,IL-18 and anti-IL-12 antibody were administered in the early phase of acute myocarditis.

Methods: BACB/C mice (n=75) were inoculated intraperitoneally with CVB₃, thereafter IL-12 (10ng/mouse/day) and IL-18 (1ug/mouse/day) were used singly or together on day 0 to 4 (each group n=15), control group (CVB₃ infected, n=20) was treated with same dose PBS, anti-IL-12 antibody (0.1mg/mouse/day, n=10) was used on day 0 to 1. Mice were sacrificed at day 1,3,5,7, the protein concentration of IL-12,IL-18, IFN-��in serum and myocardium were quantitated by ELISA.IL-12 mRNA expression in the hearts was detected by RT-PCR. Meanwhile, the splenocytes were prepared and the cytotoxicity of NK cell was assayed. The viral titer in myocardium tissue were tested, and myocardium pathology was observed under optical microscope.

Results: The protein concentration of IL-12,IL-18 and IFN-��were higher in serum and myocardium after CVB₃ inoculation, and NK activity enhanced.After IL-12 and IL-18 were administered, IFN-��production increased more significantly. NK activity reached peak on

day 3 and persist in high level (data not shown). At the same time, viral titer in myocardium decreased, myocardium inflammation mitigatede, and mouse survival rate was increased markedly (86.7%, 100% respectively, control group was 66.7%).But in anti-IL-12 antibody treated group, NK activity reached peak on day 5, the production of IFN-��were lower and myocardium inflammation was more serious than that of IL-12 treated group, although there was no statistical difference of survival rate between two group (anti-IL-12 antibody group was 80%) .

Conclusion: Both of IL-12 and IL-18 have protective role in mouse viral myocarditis, and they have synergistic effect. IL-18 seems more effective than IL-12.

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