INTERLEUKIN-13 EFFECTIVELY DOWN-REGULATES THE MONOCYTE INFLAMMATORY POTENTIAL DURING TRAUMATIC STRESS

Qbjectives: To determine the potential of interleukin-13 (IL-13) to mo dify in vitro lipopolysaccharide-induced monocyte-macrophage (MO) acti vity in human cells from individuals who had sustained either major me chanical or burn injury and to investigate whether the effect of IL-13 is different on MOs that have been preactivated under traumatic stres s than on monocytic cells from healthy volunteers. Design: Peripheral MOs from 20 controls and 16 patients after major burn or mechanical tr auma were separated on days 1, 3, 5, and 7 after injury and incubated with lipopolysaccharide (1 mu g/mL) in the presence or absence of IL-1 3 (10 ng/mL) for 4 hours and for 20 hours. Thereafter, the following m easures were determined from the culture supernatants: neopterin, nitr ic oxide, tumor necrosis factor alpha, IL-1 beta, IL-6, and IL-8. Resu lts: Ex vivo lipopolysaccharide-activated MOs, compared with control c ells, displayed considerably enhanced inflammatory activity during the immediate posttraumatic course, with a substantial and consistent ele vation of levels of tumor necrosis factor alpha and IL-6. The addition of human recombinant IL-13 to the MO cultures resulted in an effectiv e down-regulation of the synthesis of tumor necrosis factor alpha, IL- 1 beta, and IL-6 as well as IL-8, showing an average reduction of medi ator production to two thirds of the value found in corresponding sole lipopolysaccharide-stimulated cultures. The impact of human recombina nt IL-13 on control MOs was almost identical for IL-6 and IL-1 beta, s lightly lower for IL-8, and nonexistent for tumor necrosis factor alph a. Conclusion: From this study and preexisting findings, we conclude t hat, based on its biologic properties, IL-13 should be tested as a bio logic response modifier for acute states of trauma-induced host defens e deficiency.