Could interferon-gamma be a therapeutic target for treating heart failure? - PubMed (original) (raw)

Review

Could interferon-gamma be a therapeutic target for treating heart failure?

Scott P Levick et al. Heart Fail Rev. 2014 Mar.

Abstract

The cytokine interferon-gamma (IFN-γ) is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. While a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will (1) discuss the source of IFN-γ in the diseased heart; (2) summarize the data from animal studies; (3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; (4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and (5) present the clinical evidence supporting a role for IFN-γ in heart failure.

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Conflict of interest statement

Disclosures:

Drs. Scott Levick and Paul Goldspink have no conflicts of interest or financial ties to disclose.

Figures

Figure 1

Figure 1

Schematic summarizing the beneficial and adverse effects attributed to IFN-γ in the heart. Adverse stimuli, such as myocarditis or hypertension, initiate the release of IFN-γ from inflammatory cells recruited into the heart. Multiple studies have concluded that IFN-γ initiates adverse effects on cardiac fibroblasts, leading to fibrosis, and cardiomyocytes, leading to hypertrophy. Other studies have alternatively found that IFN-γ exerts protective effects limiting cardiac hypertrophy. ANF, atrial natriuretic factor; MHC, myosin heavy chain.

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