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Open Access 01-12-2021 | Coxsackievirus | Research

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Authors: Yimin Xue, Mingguang Chen, Qian Chen, Tingfeng Huang, Qiaolian Fan, Fenghui Lin, Jun Ke, Feng Chen

Published in: Virology Journal | Issue 1/2021

Abstract

Background

Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated.

Methods

Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected.

Results

The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication.

Conclusions

Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

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Title: Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
Authors: Yimin Xue
Mingguang Chen
Qian Chen
Tingfeng Huang
Qiaolian Fan
Fenghui Lin
Jun Ke
Feng Chen
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Coxsackievirus
Myocarditis
Cytokines
Published in: Virology Journal / Issue 1/2021
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-021-01687-w

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Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Abstract

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Methods

Results

Conclusions

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Abstract

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