Production of interleukin-12 is under the control of endogenous interleukin-10 in myocardial ischemia-reperfusion

Interleukin (IL)-12 is a heterodimeric cytokine that is secreted mainly by antigen-presenting cells and plays a key role in determining the nature of immune response to exogenous or endogenous antigens. Negative regulators of IL-12 production include IL-10. With use of wild-type and IL-10-deficient mice, the aim of the current investigation was to determine whether IL-12 is produced in myocardial reperfusion injury and whether endogenous IL-10 modulates its production. IL-10 levels were significantly higher than baseline at both 2 h and 6 h after the start of the reperfusion. In the IL-10-deficient animals, no IL-12 could be detected in the plasma. In the wild-type animals, at baseline, and at 1-6 h after myocardial ischemia-reperfusion, no detectable increases in IL-12 were measured. However, in the IL-10-deficient mice, a significant and pronounced increase in IL-12 was detected. IL-10-deficient mice also exhibited significantly higher mortality during reperfusion than wild-type animals. We conclude that the production of IL-12 in myocardial reperfusion injury is dramatically affected by the levels of endogenous IL-10.