Update on coxsackievirus B3 myocarditis

Abstract

Purpose of review: To present recent findings on the pathogenesis of coxsackievirus B3 (CVB3) myocarditis based on animal models, with a focus on the role of T helper (Th) immune responses in disease progression.

Recent findings: Acute CVB3 myocarditis is known to be increased by Th1 immune responses, but recent findings indicate that Th1-type immunity protects against acute myocarditis by reducing viral replication and prevents the progression to chronic myocarditis and dilated cardiomyopathy (DCM) by inhibiting Th2 responses. Th2 responses reduce acute myocarditis by inhibiting Th1 responses via regulatory T cells and anti-inflammatory cytokines, but can be deleterious when they induce acute cardiac remodeling leading to chronic myocarditis/DCM. Th2-skewed immune responses allow resistant strains of mice to progress from myocarditis to DCM. In contrast, Th17 responses are elevated during acute and chronic myocarditis and have been found to contribute to cardiac remodeling and DCM.

Summary: Recent data indicate that elevated Th2 and Th17 responses during acute CVB3 myocarditis are critical for the progression from myocarditis to DCM and heart failure because of their ability to induce cardiac remodeling. Th1 responses protect against CVB3 myocarditis by inhibiting Th2 responses and viral replication, but increase acute inflammation.

Figure 1. Role of IL-23/p40 in CVB3 myocarditis

Male WT BALB/c and IL-12p40 deficient (p40−/−) mice were inoculated ip with 10³ PFU of heart-passaged CVB3+heart proteins on day 0 and A) myocarditis, B) viral replication, and C) cytokines assessed at day 10 pi. IL-23/p40 deficiency did not alter myocarditis, viral replication or cytokine levels in the heart, except for reducing IL-12/IL-23p40 levels. Data show the mean ±SEM from one of three experiments using 7–10 mice/group. P values were evaluated using the Student’s t and/or Mann-Whitney rank tests.