title: Hypertonic saline resuscitation restores hemorrhage-induced immunosuppression by decreasing prostaglandin E2 and interleukin-4 production.
abstract: It was previously shown that hypertonic saline (HTS) enhances in vivo and in vitro cellular immune function of normal mice and reverses in vitro prostaglandin E2 (PGE2)-induced immunosuppression of normal peripheral blood mononuclear cells. Hemorrhage induces immunosuppression despite adequate isotonic fluid resuscitation. The effects of HTS resuscitation on immunosuppression following hemorrhage were studied. A mouse model of hemorrhagic shock was used. Bleeding was performed through a catheter placed in the femoral artery. Phytohemagglutinin-induced splenocyte proliferation and interleukin (IL)-1, IL-2,IL-4, IL-6, IL-10, transforming growth factor beta, and PGE2 plasma levels were measured 2 and 24 hr following hemorrhage and resuscitation with lactated Ringer's and HTS. In vivo cellular immune function was measured using a contact hypersensitivity test. Suppression of splenocyte proliferation (40%) 24 hr following hemorrhage occurred after lactated Ringer's resuscitation. HTS prevented immunosuppression. In vivo cell-mediated immune function 24 hr after hemorrhage was improved by HTS. HTS-resuscitated animals showed significantly lower levels of IL-4 and PGE2, and slightly elevated levels of proinflammatory cytokines (IL-1, IL-2, and IL-6). HTS reverses hemorrhage-induced T-cell suppression by reducing the production and/or release of IL-4 and PGE2.
authors.affiliation: Department of Surgery, University of California, San Diego, 92103-8896, USA.
authors.forename: R
authors.initials: R
authors.lastname: Coimbra
authors.forename: W G
authors.initials: WG
authors.lastname: Junger
authors.forename: D B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: F C
authors.initials: FC
authors.lastname: Liu
authors.forename: W H
authors.initials: WH
authors.lastname: Loomis
authors.forename: M F
authors.initials: MF
authors.lastname: Evers
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood*; D006439:Hemodynamics / Q000502:physiology; D006470:Hemorrhage / Q000276:immunology*; D006982:Hypertonic Solutions; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007552:Isotonic Solutions / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012151:Resuscitation; D000077325:Ringer's Lactate; D012964:Sodium / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D006982:Hypertonic Solutions; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D012965:Sodium Chloride; D012964:Sodium; D015232:Dinoprostone