The role of proinflammatory cytokines in the generation of myocardial ischemia/reperfusion injury

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Proinflammatory cytokines, especially tumor necrosis factor-α (TNF-α) are thought to be involved in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. However, their precise role in I/R injury is still unknown. The heart was exposed by left lateral thoracotomy and the left coronary artery was occluded for 30 minutes, then reperfused for 120 minutes in TNF-α knockout (KO) and wild-type (WT) mice. The infarct size in TNF-α KO was significantly reduced compared with WT mice. The frequency of arrhythmia was decreased and cardiac function during reperfusion was significantly improved in TNF-α KO compared with those in WT. The activation of NE-κB, the expressions of chemokines and adhesion molecules, and the infiltration of leukocytes were also significantly reduced in TNF-α KO compared with WT. These findings provide evidence that TNF-α aggravates I/R injury. TNF-α exacerbates myocardial I/R injury at an early stage of reperfusion by activating NE-κB, thereby inducing chemokines and adhesion molecules, and facilitating leukocyte infiltration. However, after permanent coronary occlusion, infarct size was slightly but significantly smaller in WT mice than TNF-α KO mice. WT and TNF-α KO mice were irradiated and the bone marrow cells from GFP transgenic mice were transplanted. After I/R, GFP positive cells were detected in the infarct area and the number of GEP positive cells was significantly increased in TNF-α KO mice than WT mice.