The potential pathophysiological roles of proinflammatory cytokines in heart diseases

Abstract

Proinflammatory cytokines, in particular TNF-alpha, IL-1beta and IL-6, are believed to be involved in the progression of cardiac remodeling in heart diseases. However, multi-center clinical trial failed to show beneficial role of anti-cytokine treatment in patients with heart diseases suggesting that the roles of cytokines in heart diseases are still elusive. The present study thus investigated the potential pathophysiological roles of proinflammatory cytokines in response to acute cardiac injuries and the following cardiac remodeling processes. The present study first showed the upregulation of the proinflammtory cytokines around the sinoatrial node in response to atrial infarction and the upregulated cytokines may be linked to the onset of cardiac arrhythmia in clinics; The present study subsequently showed that persistent volume overload could induce the upregulation of IL-1beta and IL-6 in the subendocardium, but not TNF-alpha suggesting that TNF-alpha was not involved in the progression of volume overload- induced cardiac remodeling; The present study then demonstrated that acute cardiac injuries not only induced the activation of cytokines in the heart but also in the spinal cord, a location which current anti-cytokine therapy cannot reach. Overall, the present study suggested, for the first time, that the investigation of cytokines in heart diseases should also be extended to the CNS, where current antagonists of cytokines cannot reach.