Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart.

BACKGROUND

Several investigations have implicated cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, IL-8 and transforming growth factor-beta in the pathophysiology of cellular dysfunction in ischemia-reperfusion (I/R). Although an increase in the production of these cytokines has been detected after myocardial infarction and cardiopulmonary bypass surgery, their exact role and mechanisms for inducing cardiac dysfunction are poorly understood.

OBSERVATIONS

TNF-alpha, transforming growth factor-beta, IL-1, IL-6 and IL-8 have frequently been studied in different cardiovascular diseases, including I/R injury in the heart. Low concentrations of TNF-alpha appear to exert cardioprotective effects, whereas high concentrations have been shown to produce deleterious actions in the heart. Some efforts have been made to explore the molecular mechanisms of cytokine actions; however, such information is insufficient to develop therapeutic strategies to combat their deleterious effects during the development of I/R injury in the heart.

CONCLUSIONS

In addition to a time-dependent response, the conflicting effects of cytokines seem to depend on their concentrations used in different experimental studies. It is also likely that both the beneficial and pathophysiological actions of cytokines occur concomitantly. On the basis of the existing literature, it is suggested that different ways need to be found to modify the synthesis as well as the cardiodepressant actions of cytokines to improve the therapy of ischemic heart disease.