We examined the role of IL-6 in the temporal development of cardiac ischemia-reperfusion injury employing a closed-chest I/R model. Infarction, local and systemic inflammation, neutrophil infiltration, coagulation and ST elevation/resolution were compared between wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice after 1 h ischemia and 0, A1/2, 3, and 24 h reperfusion. IL-6 deficiency reduced infarct size at 3 h reperfusion (28.8 +/- A 4.5 % WT vs 17.6 +/- A 2.5 % IL-6(-/-)), which reduction persisted and remained similar at 24 h reperfusion (25.1 +/- A 3.0 % WT vs 14.6 +/- A 4.4 % IL-6(-/-)). Serum Amyloid A was reduced at 24 h reperfusion only (57.5 +/- A 4.9 WT vs 24.8 +/- A 5.6 ug/ml IL-6(-/-) mice). Cardiac cytokines (IL-6, IL-1 beta and TNF alpha) peaked at 3 h reperfusion, but IL-1 beta and TNF alpha levels were unaffected by IL-6 deficiency. Significant neutrophil influx was only detected at 24 h reperfusion and was similar for WT and IL-6(-/-). Tissue factor peaked at 24 h reperfusion, whereas fibrin/fibrinogen peaked at 3 h reperfusion and was completely resolved at 24 h reperfusion; both coagulation factors were unaltered by IL-6 deficiency. Prolonged ST elevation was observed during ischemia that completely resolved for both genotypes at early reperfusion. The data suggest that, in the absence of major surgical intervention, IL-6 contributes to the development of infarct size in the early phase of reperfusion; this contribution did not depend on neutrophil influx, IL-1 beta and TNF alpha, tissue factor and fibrin.
- Closed-chest model
- Ischemia/reperfusion injury