DISTINCT MECHANISMS OF IMMUNOSUPPRESSION AS A CONSEQUENCE OF MAJOR SURGERY

Altered host defense mechanisms after major surgery or trauma are cons idered important for the development of infectious complications and s epsis. In the present study, we demonstrate that major surgery results in a severe defect of T-lymphocyte proliferation and cytokine secreti on in response to coligation of the antigen receptor complex and CD28. During the early postoperative course, reduced cytokine secretion was observed for interleukin-2 (IL-2), gamma interferon, and tumor necros is factor alpha, which are associated,vith the Th1 phenotype of helper T lymphocytes, and for IL-4, the index cytokine of Th2 cells. During the late postoperative course, T-cell cytokine secretion increased to normal levels, Production of the anti-inflammatory cytokine IL-IO was altered, with different kinetics being selectively elevated during the late postoperative course. In contrast, the capacity of peripheral bl ood monocytes to present bacterial superantigens and to stimulate T-ce ll proliferation was normal or enhanced after surgery despite a signif icant loss of cell surface HLA-DR molecules. Thus, the level of major histocompatibility complex class II protein expression does not appear to predict the antigen-presenting capacity of monocytes obtained from surgical patients with uneventful postoperative recovery. Secretion o f IL-1 beta and IL-10 by endotoxin-stimulated peripheral blood monocyt es was increased at different time points after surgery, Major surgery therefore results in a distinct pattern of immune defects with a pred ominant defect in the T-cell response to T-cell receptor- and CD28 cor eceptor-mediated signals rather than an impaired monocyte antigen-pres enting capacity. Suppression of T-cell effector functions during the e arly phase of the postoperative course may define a state of impaired defense against pathogens and increased susceptibility to infection an d septic complications.