1. Lack of IL-6 during Coxsackievirus Infection Heightens the Early Immune Response Resulting in Increased Severity of Chronic Autoimmune Myocarditis.
- Author
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Poffenberger, Maya C., Straka, Nadine, Warry, Nahida El, Fang, Dianne, Shanina, Iryna, and Horwitz, Marc S.
- Subjects
MYOCARDITIS ,IMMUNE response ,ENTEROVIRUS diseases ,PREVENTIVE medicine ,COXSACKIEVIRUS diseases ,IMMUNOLOGIC diseases ,AUTOANTIBODIES ,T cells ,CHEMOKINES - Abstract
Background: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL)-6 is integral to the development of experimental-induced autoimmune myocarditis. However, the function of IL-6 during viral-mediated autoimmunity has yet to be elucidated. Methods and Results: To address the requirement of IL-6 during disease induction, IL-6 deficient mice were infected with coxsackievirus B3 (CB3). Following infection, mice lacking IL-6 developed increased chronic autoimmune disease pathology compared to wild type controls without a corresponding change in the level of viral replication in the heart. This increase in disease severity was accompanied by elevated levels of TNF-α , MCP-1, IL-10, activated T cells and cardiac infiltrating macrophage/monocytes. Injection of recombinant IL-6 early following infection in the IL-6 deficient mice was sufficient to lower the serum cytokines TNF-α and IL-10 as well as the serum chemokines MCP-1, MIP-1β, RANTES and MIG with a corresponding decrease in the chronic disease pathology strongly suggests an important regulatory role for IL-6 during the early response. Conclusions: While IL-6 plays a pathogenic role in experimental-induced autoimmune disease, its function following viral-induced autoimmunity is not reprised. By regulating the early immune response and thereby controlling the severity of chronic disease, IL-6 directs the outcome of chronic autoimmune myocarditis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2009
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