Interleukin-10 Prevents Early Cytokine Release in Severe Intraabdominal Infection and Sepsis

• Published in: The Journal of surgical research 1997-07, Vol.70 (2), p.107-112
• Main Authors: Rongione, Anthony J., Kusske, Amy M., Ashley, Stanley W., Reber, Howard A., McFadden, David W.
• Format: Article
• Language: English
• Subjects: Abdomen, Acute - physiopathology; Acute Disease; Animal infectious diseases; Animals; Biological and medical sciences; Cecum - injuries; Female; General aspects; Infectious diseases; Interleukin-1 - blood; Interleukin-10 - pharmacology; Interleukin-6 - blood; Intestinal Diseases - physiopathology; Medical sciences; Mice; Sepsis - physiopathology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1997.5071

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in animals is a model that closely mimics the physiologic changes seen in human sepsis. Four groups of 14 female Swiss–Webster mice were used. Group 1 underwent laparotomy alone. groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as control vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following CLP. Serum TNF-α, IL-1β, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). CLP produced a significant rise in serum TNF, IL-6, and IL-1 in 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 systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.