[Protective effect and mechanism of IL-17 monoclonal antibody on mice with viral myocarditis]

To explore the protective effects of interleukin-17 monoclonal antibody (IL-17 mAb) on viral myocarditis (VMC) mice and its possible molecular mechanisms.

Ninety BALB/c mice were randomly divided into 4 groups: normal control group (n=15), model group (n=25), isotype control group (n=25) and IL-17 mAb group (n=25). Mice in model, isotype control and IL-17 mAb groups were inoculated with 0.1 mL Eagle's solution containing Coxsackievirus B3 (CVB3) intraperitoneally; and those in normal control group were treated with 0.1 mL Eagle's solution without CVB3. On the day 3 and 5 after inoculation, mice in isotype control and IL-17 mAb groups received intragastric administration of 100 μg non-specific IgG antibody and IL-17 mAb, respectively. On day 7 postinoculation, 5 mice were killed in each group, and the hearts were removed. Virus titer was detected using Reed-Muench method, and CVB3 mRNA copy number was measured by real-time quantitative PCR. All mice were killed on day 14 after weighing body mass (BM). The mortality was compared among groups. Serum was separated and serum cardiac troponin I (cTnI) concentration was detected using ELISA. The heart was removed and weighed to calculate heart index (HM/BM). Histological sections of heart were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. The expression of nuclear factor-κB (NF-κB) p65 was examined by Western blotting. Myocardial interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected by ELISA.

The HM/BM, serum cTnI concentration, NF-κB p65 expression level and myocardial IL-6 and TNF-α contents in model group were higher than those in normal control group (P<0.01). In comparison with model and isotype control groups, mortality, HM/BM, serum cTnI concentration, myocardial histopathologic scores, virus titer, CVB3 mRNA copy number, NF-κB p65 expression level, and myocardial IL-6 and TNF-α contents in IL-17 mAb group were significantly reduced (P<0.05 or 0.01). There was no difference in the above indicators between isotype control group and model group(P>0.05).

IL-17 mAb can improve myocardial injury in VMC mice, and the mechanisms are associated with the inhibition of viral replication and NF-κB activation.