Mechanism of Enhanced Susceptibility to Sepsis Following Hemorrhage: Interleukin-10 Suppression of T-Cell Response Is Mediated by Eicosanoid-Induced Interleukin-4 Release

Academic Article

Abstract

  • Decreased splenocyte/T-cell proliferation was associated with enhanced release of IL-10 by cells from hemorrhaged mice. However, unlike T cells, IL-10 release by macrophages was not comparatively elevated. While no changes were seen in systemic plasma levels of IL-10, the role of IL-10 as a localized immunosuppressant was demonstrated by the ability of IL-10 monoclonal antibody to restore T-cell proliferation following hemorrhage. Furthermore, elevated IL-10 release was prevented by the addition of ibuprofen or monoclonal antibody against transforming growth factor β or IL-6. Since these agents have direct or indirect influences on prostanoid synthesis, studies were carried out examining the capacity of varying concentrations of prostaglandin E2 (PGE2) to augment IL-10 release by murine cloned Th2 cells (D10.G4.1) and by T cells from sham-operated or hemorrhaged mice. While the addition of PGE2, 10−9 mol/L, potentiated the release of IL-10, this effect appears to be indirect, since the incorporation of monoclonal antibody to IL-4 prevented the release of IL-10 by PGE2-treated cells from sham-operated or hemorrhaged mice. Such a mechanism of eicosanoid-induced IL-4/IL-10 cell-mediated immunosuppression may directly contribute to the decreased capacity to ward off infectious challenge seen following hemorrhage. (Arch Surg. 1994;129:1172-1178). © 1994, American Medical Association. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Ayala A; Lehman DL; Herdon CD; Chaudry IH
  • Start Page

  • 1172
  • End Page

  • 1178
  • Volume

  • 129
  • Issue

  • 11