IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice

Kong,Qing; Xue,Yimin; Wu,Weifeng; Yang,Fan; Liu,Yanli; Gao,Mengsha; Lai,Wenyin; Pan,Xiaofen

doi:10.3892/mmr.2013.1323

IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice

Authors:
- Qing Kong
- Yimin Xue
- Weifeng Wu
- Fan Yang
- Yanli Liu
- Mengsha Gao
- Wenyin Lai
- Xiaofen Pan
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Affiliations: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning, Guangxi 530021, P.R. China
Published online on: February 18, 2013 https://doi.org/10.3892/mmr.2013.1323
Pages: 1329-1335

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Abstract

Interleukin (IL)-22 has either proinflammatory or tissue‑protective properties, depending on the nature of the affected tissue and the local cytokine milieu, including the presence or absence of IL-17A co-expression. We have previously demonstrated that IL-22 has critical anti-inflammatory and antiviral roles in mice with coxsackievirus B3 (CVB3)‑induced acute viral myocarditis (AVMC) in the presence of IL-17A. However, whether IL-17A determines the function of IL-22 in AVMC remains unknown. Therefore, the present study, in continuation of our previous investigations, aimed to determine whether IL-22 plays a distinctly different role in the absence of IL-17A in AVMC by using IL-17A-deficient mice. Results demonstrated that the neutralization of IL-22 in IL-17A‑deficient mice alleviated the severity of myocarditis. This was demonstrated by the lower pathological scores of heart sections and ratios of heart weight/body weight (HW/BW), reduced production of activator of transcription 3 (STAT3) and proinflammatory cytokines TNF-α and IL-6, followed by increased viral replication and decreased levels of the antiviral cytokine IFN-γ. Furthermore, the correlation between cardiac CVB3 RNA and IL-22 mRNA or IFN-γ mRNA was negative. In conclusion, IL-22 exacerbated the severity of AVMC and restrained viral replication in the absence of IL-17A. Spleen lymphocytes cultured with recombinant IL-17 (rIL-17) increased the production of IL-22. Combined with our previous data, these results indicate that IL-17A is not involved in regulating the antiviral role, however, may mediate the tissue-protective versus pathogenic properties of IL-22 in CVB3-induced AVMC in mice.

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