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Am J Physiol Cell Physiol 281: C840-C848, 2001;
0363-6143/01 $5.00
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Vol. 281, Issue 3, C840-C848, September 2001

Hypertonicity rescues T cells from suppression by trauma-induced anti-inflammatory mediators

William H. Loomis, Sachiko Namiki, David B. Hoyt, and Wolfgang G. Junger

Surgical Immunology Research Laboratory, Division of Trauma, Department of Surgery, University of California San Diego, San Diego, California 92103-8236

Trauma causes the release of anti-inflammatory factors thought to cause infections by inhibiting T cells. We have found that hypertonic saline (HS) enhances functions of normal T cells. Here we studied if HS can rescue T cells from suppression by costimulating interleukin (IL)-2 production. Human peripheral blood mononuclear cells were treated with the immunosuppressive factors IL-4, IL-10, transforming growth factor (TGF)-beta 1, and PGE2 and with serum of trauma patients and stimulated with phytohemagglutinin, and IL-2 production was measured. Costimulation with HS tripled IL-2 production of normal cells. IL-4, IL-10, TGF-beta 1, and PGE2 suppressed IL-2 production with IC50 of 500, 1, 36,000, and 0.01 pg/ml, respectively. Costimulation of suppressed cells with HS restored IL-2 production and increased IC50 values >70-fold. Serum from trauma patients could completely suppress normal cells; however, costimulation with HS restored IL-2 production by up to 80% of the control response. These findings show that HS can restore the function of suppressed T cells, suggesting that HS resuscitation of trauma patients could reduce posttraumatic sepsis.

interleukin-2 expression; immune suppression; p38 mitogen-activated protein kinase; small volume resuscitation; T lymphocytes


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