Hypertonic saline resuscitation restores hemorrhage-induced immunosuppression by decreasing prostaglandin E(2) and interleukin-4 production

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 E(2) (PGE(2))-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 PGE(2) 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 PGE(2), 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 PGE(2). (C) 1996 Academic Press, Inc.