REDUCED EX-VIVO INTERLEUKIN-8 PRODUCTION BY NEUTROPHILS IN SEPTIC ANDNONSEPTIC SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

Ex vivo cytokine production by circulating lymphocytes and monocytes i s reduced in patients with infectious or noninfectious systemic inflam matory response syndrome. Very few studies have addressed the reactivi ty of polymorphonuclear cells (PMN), To analyze further the relative c ontribution of systemic inflammatory response syndrome alone or in com bination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis, Cells were acti vated with either lipopolysaccharide (LPS) or heat-killed streptococci . Compared with healthy controls, the release of IL-8 by PMN in both g roups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed strep tococci, These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reac tivity of circulating PMN, We investigated whether the observed dimini shed reactivity of PMN might reflect an endotoxin tolerance phenomenon . Our in vitro experiments with PMN from healthy controls indicated th at PMN could not be rendered tolerant stricto sensu, However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients. (C) 1998 by The American Society of Hematology.