INTERLEUKIN-10 PREVENTS EARLY CYTOKINE RELEASE IN SEVERE INTRAABDOMINAL INFECTION AND SEPSIS

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are import ant in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokin e release from activated macrophages. The aim of this study was to det ermine if IL-10 would decrease serum cytokine elevation in a murine mo del of cecal ligation and puncture (CLP). CLP in animals is a model th at closely mimics the physiologic changes seen in human sepsis. Four g roups of 14 female Swiss-Webster mice were used. Group 1 underwent lap arotomy alone. groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as c ontrol vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) receive d 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Anim als were sacrificed at 3 and 9 hr following CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked immunosorbent assay ( ELISA). CLP produced a significant rise in serum TNF, IL-6, and IL-1 i n untreated controls. Prophylactic or therapeutic administration of IL -10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemi c rise in macrophage-derived cytokines and (2) IL-10 given either befo re or after che onset of CLP-induced intraabdominal infection and seps is is able to inhibit this early release of macrophage-derived systemi c mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis. (C) 1997 Academic P ress.