Cytokine inhibiting therapies demonstrated beneficial effects in animal models of myocardial infarction and heart failure, but larger clinical studies have yielded mostly unsatisfactory results.
Do cytokine inhibiting therapies improve cardiac function and outcomes in acute myocardial infarction and chronic heart failure?
Despite promising experimental data for cytokine inhibition in acute MI and chronic HF, clinical translation has been largely disappointing, highlighting the need for further evaluation.
Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome. On the other hand, neutral or even detrimental results have been reported for some (IL-1, IL-6, IL-8, and MCP-1). Ambivalence of cytokine function, differences in study designs, treatment regimens and chosen endpoints hamper the translation of experimental research into clinical practice. Human studies are currently limited to IL-1β inhibition, IL-1 receptor antagonists (IL-1RA), IL-6 receptor antagonists (IL-6RA) or TNF inhibition. Despite favorable effects on cardiovascular events observed in retrospective cohort studies of rheumatoid arthritis patients treated with TNF inhibition or IL-1RA, most prospective studies reported disappointing and inconsistent results. Smaller studies (n 100) evaluating IL-1β inhibition presented positive results on outcome. In conclusion, of the 10 anticytokine therapies tested in animals models beneficial effects have been reported in at least one setting. In larger clinical studies, findings were unsatisfactory in all but one. Many anticytokine therapies with promising animal experimental data continue to require further evaluation in humans.
Hartman et al. (Thu,) conducted a review in Acute myocardial infarction and chronic heart failure. Cytokine inhibiting therapies was evaluated. Cytokine inhibiting therapies demonstrated beneficial effects in animal models of myocardial infarction and heart failure, but larger clinical studies have yielded mostly unsatisfactory results.
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