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November 1994

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

Author Affiliations

From the Shock and Trauma Research Laboratories, Department of Surgery (Drs Ayala and Chaudry and Mss Lehman and Herdon), Microbiology (Dr Ayala), and Physiology (Dr Chaudry), Michigan State University, East Lansing.

Arch Surg. 1994;129(11):1172-1178. doi:10.1001/archsurg.1994.01420350070009

Objectives:  To determine (1) whether interleukin-10 (IL-10) contributes to depressed T-cell responses observed following hemorrhage and (2) what effect other immunosuppressive agents known to play a role in hemorrhage have on IL-10 release.

Design:  Hemorrhage was induced in C3H/HeN mice. The mice were resuscitated and then killed 2 hours after hemorrhage to obtain plasma, splenocytes, splenic macrophages, and splenic T cells.

Results and Conclusions:  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)

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