Review ArticleThe varying faces of IL-6: From cardiac protection to cardiac failure

- IL6 is cardio protective during acute insult to the myocardium.
- IL6 transitions to a pathogenic factor when it remains elevated chronically.
- The transition is associated with specific downstream signaling unique to IL6.
- Chronic IL6 signaling is associated with heart failure.
- In myocarditis chronic IL6 signaling contributes to progression to dilated cardiomyopathy.

IL6 is a pleiotropic cytokine that is made in response to perturbations in homeostasis. IL6 becomes elevated in the acute response to host injury and can activate immune cells, direct immune cell trafficking, signal protective responses in local tissue, initial the acute phase response or initiate wound healing. In the short term this proinflammatory response is protective and limits host damage. It is when this acute response remains chronically activated that IL6 becomes pathogenic to the host. Chronically elevated IL6 levels lead to chronic inflammation and fibrotic disorders. The heart is a tissue where this temporal regulation of IL6 is very apparent. Studies from myocardial infarction show how short-term IL6 signaling can protect and preserve the heart tissue in response to acute damage, where long term IL6 signaling or an over-production of IL6R protein plays a causal role in cardiovascular disease. Thus, IL6 can be both protective and pathogenic, depending on the kinetics of the host response.