No abstract

No abstract

Serum IL-10 levels on admission enabled one to predict subsequent CS requiring MCSS and mortality of fulminant myocarditis patients.

Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.

Background-Viral myocarditis follows a fatal course in ≈30% of patients. Interleukin-1 receptor-associated kinase 4 (IRAK4), a major nodal signal transducer in innate immunity, can play a pivotal role in host inflammatory response. We sought to determine how IRAK4 modulates inflammation and outcome in a mouse model of viral myocarditis. Methods and Results-Myocarditis was induced after intraperitoneal inoculation of coxsackievirus B3 into C57Bl/6 IRAK4-deficient mice and their littermate controls. Mortality and viral proliferation were markedly reduced in IRAK4−/− mice compared with their IRAK4 +/+ littermates. Disease resistance of IRAK4 −/− mice paralleled increased amounts of protective heart-infiltrating CCR5 + monocytes/macrophages and enhanced interferon-α and interferon-γ production 2 days after infection. Competitive bone marrow chimera demonstrated that intact IRAK4 function inhibited heart-specific migration of bone marrow-derived CCR5 + cells. Mechanistically, lack of IRAK4 resulted in interferon regulatory factor 5 homodimerization via reduced melanoma differentiation-associated protein 5 degradation and enhanced Stat1 and Stat5 phosphorylation. Consequently, antiviral interferon-α and interferon-γ production, as well as CCR5 + cell recruitment, increased, whereas the overall proinflammatory response was drastically reduced in the absence of IRAK4. Conclusions-Innate immunity signal transducer IRAK4 exacerbates viral myocarditis through inhibition of interferon production and reduced mobilization of protective CCR5 + monocytes/macrophages to the heart. The combination of IRAK4 inhibitors and antiviral adjuvants may become an attractive therapeutic approach against viral myocarditis in the future.