POLYMORPHONUCLEAR LEUKOCYTE SUPEROXIDE ANION GENERATION IN CRITICALLY ILL CHILDREN

Generation of active oxygen species by activated PMNs plays a paramont role in human immunologic defenses. However, numerous in vitro experiments have demonstrated that inadvertant release of highly reactive oxygen metabolites by the PMN into the surrounding milieu results in autoinjury and is associated with diffuse capillary leak syndromes (septic shock, ARDS). NADPH oxidoreductase, the superoxide anion generating enzyme, is a PMN membrane bound flavoprotein normally dormant but inducible by a variety of agents. We studied the specific activity of this enzyme in critically ill children to determine if detection of its activation might provide an early clue of impending in inflammatory amplification injury. Venous blood specimens from 12 healthy young adult controls reflected an induced enzyme activity of 8.23 ± 2.1 nmoles superoxide/min./10(6) PMNs ± S.D. Similarly the induced activity in a group of 6 pediatric intensive care patients without evidence of capillary leak syndrome was 7.3 ± 2.2 . In constrast the mean induced activity from a group of 6 critically ill children with evidence of capillary leak syndrome was 3.0 ± 1.1 (p<.001). No activity was demonstrated in non-induced PMNs from any group. No differences in induced enzyme activity were appreciated between venous and arterial blood samples. Such findings may demonstrate the phenomena of desensitization of previously in vivo activated neutrophils to additional stimulation, and may represent a host defense which minimizes autoinjury.