Inflammation and inflammatory cytokines in cardiac cachexia: an incendiary issue

Cardiac cachexia, a severe consequence of heart failure, is marked by progressive weight loss due to skeletal and cardiac muscle wasting. This complex condition involves nutritional deficiencies, gut dysfunction, hormonal imbalances, and a critical disruption in muscle protein metabolism. However, chronic inflammation in the heart failure is the key driver, triggering the release of cytokines like TNF-α, IL-6, IL-1, IL-10 and TGF-β. These cytokines significantly impact muscle metabolism, promoting protein breakdown while hindering protein synthesis. Elevated TNF-α levels induce anorexia, worsening weight loss, and muscle depletion. IL-6 acts as a potent muscle-wasting agent, upregulating protein degradation via the ubiquitin-proteasome system. Similarly, IL-1 activates pathways that promote protein breakdown and suppress cell proliferation. TGF-β, despite its diverse functions, contributes to muscle atrophy by increasing protein degradation. In contrast, the anti-inflammatory cytokine IL-10 promotes protein synthesis by suppressing pathways that normally inhibit it. Understanding these cytokine actions provides valuable insights into cardiac cachexia and paves the way for targeted therapies aimed at modulating these pathways to prevent or reverse muscle wasting in heart failure. In this review, we will describe the pathophysiology of cardiac cachexia and the role of various cytokines in cardiac cachexia which is released due to inflammation.