Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian, People's Republic of China.
The Fourth Department of Intensive Care Unit, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, People's Republic of China.
Virol J. 2021 Nov 14;18(1):220. doi: 10.1186/s12985-021-01687-w.
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.
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.
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.
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.
白细胞介素 (IL)-38 是白细胞介素 1 家族的新成员，据报道它与多种与病毒感染相关的疾病有关。然而，IL-38 在急性病毒性心肌炎 (AVMC) 中的表达和功能作用尚未被研究。
雄性 BALB/c 小鼠通过腹腔 (i.p.) 注射柯萨奇病毒 B3 (CVB3) 建立 AVMC 模型。在注射后第 7 天，测量 IL-38 和 IL-36R（IL-36 受体）的表达。然后，用 i.p. 注射小鼠抗 IL-38 抗体（Abs）中和 IL-38。记录小鼠的存活率、体重减轻、心功能和心肌炎严重程度。通过流式细胞术、RT-qPCR 和 ELISA 分别测定脾 Th1 和 Th17 细胞的百分比、Th1/Th17 相关主转录因子 (T-bet 和 RORγt) 和细胞因子的表达水平。进一步检测心脏病毒复制。
AVMC 小鼠心肌和血清中 IL-38 的 mRNA 和蛋白表达水平以及心脏 IL-36R mRNA 水平均显著升高。增加的 IL-38 水平与 AVMC 的严重程度呈负相关。中和 IL-38 加重了 CVB3 诱导的 AVMC，表现为存活率降低、心功能受损、持续体重减轻以及 HW/BW 和心脏病理评分升高。此外，中和 IL-38 抑制 Th1 细胞分化，促进 Th17 细胞分化，伴有 T-bet mRNA 表达降低和 RORγt 表达升高。在 IL-38 中和组中，还观察到心肌和血清中 IFN-γ mRNA 和蛋白表达水平下调以及 IL-17、TNF-α 和 IL-6 mRNA 和蛋白表达水平上调。此外，中和 IL-38 显著促进了心脏病毒复制。
中和 IL-38 加重了 CVB3 诱导的 AVMC 小鼠的病情，这可能归因于 Th1/Th17 细胞失衡和 CVB3 复制增加。因此，IL-38 可被视为 AVMC 的潜在治疗靶点。
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