DESENSITIZATION OF THE INFLAMMATORY RESPONSE IN HUMANS - CHANGES IN RESPONSE TO CARDIOPULMONARY BYPASS

Although circulating levels of interleukin 8 (IL-8), a potent pro-infl ammatory chemokine, and many other inflammatory mediators increase in response to cardiopulmonary bypass, only a small proportion of patient s develop a clinically significant systemic inflammatory response. The natural mechanisms that control the inflammatory response are poorly understood. To investigate the role of IL-8 in a human inflammatory mo del, 15 adult patients undergoing cardiopulmonary bypass for elective coronary artery bypass grafting were studied. Following reperfusion, p lasma IL-8 levels increased significantly from 58 pg/mL (pre-bypass) a nd 66 pg/mL (after 20 min of bypass) to 98 pg/mL (p = .02 and .04, res pectively), but this was accompanied by a concomitant threefold decrea se in the IL-8 binding affinity of circulating neutrophils (Dissociati on constant (K-L) post-reperfusion/K-L pre-bypass = 3.2; K-L post-repe rfusion/K-L after 20 min of bypass = 2.8). IL-8-triggered release of m yeloperoxidase and elastase by peripheral blood neutrophils ex vivo wa s also down-regulated following reperfusion. There were no significant changes in beta 2 integrin expression or inositol polyphosphate metab olism of peripheral blood neutrophils. These changes in receptor affin ity and neutrophil responsiveness to IL-8 may represent an important i n vivo regulatory mechanism which serves to prevent excessive tissue i njury from inflammatory triggers.