Alterations of cell-mediated immune response following cardiac surgery

Nosocomial infections in patients following cardiac surgery are frequently associated with opportunistic microorganisms indicating a dysregulation of cell-mediated immune response. The objective of this prospective randomized trial, therefore, was to investigate the mechanisms of dysregulation and the counterregulatory effects of immunomodulation. Twenty patients underwent conventional postoperative therapy, another 20 patients received indomethacin, which inhibits synthesis of the down-regulating mediator prostaglandin E2, and a further 20 patients were given thymopentin in addition to indomethacin, thereby augmenting activation and differentiation of the T-lymphocytes. The immunologic parameters studied included T-lymphocytes and monocytes as well as interleucin (IL)-1 and IL-6 synthesis by monocytes, and IL-2 and IL-6 synthesis by T-lymphocytes. Following cardiac surgery a significant, persistent reduction of T-lymphocytes and IL-2 synthesis as well as significant monocytosis could be observed. Indomethacin treatment resulted in a normalization of the cellular imbalance at the end of the first postoperative week, but IL-2 synthesis remained significantly reduced during the entire observation period. Conversely, with combined indomethacin and thymopentin treatment restoration of cellular distribution as well as protection of IL-2 synthesis could be achieved. These results indicate a quantitative and functional impairment of the forward regulation of cell-mediated immunity. It was shown for the first time that combined indomethacin and thymopentin treatment could successfully counteract these immunomechanistic alterations.