Hypertonicity rescues T cells from suppression by trauma-induced anti-inflammatory mediators.
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 PGE(2) 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 PGE(2) suppressed IL-2 production with IC(50) of 500, 1, 36,000, and 0.01 pg/ml, respectively. Costimulation of suppressed cells with HS restored IL-2 production and increased IC(50) 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.
Loomis
W H
WH
Surgical Immunology Research Laboratory, Division of Trauma, Department of Surgery, University of California San Diego, San Diego, California 92103-8236, USA.
Namiki
S
S
Hoyt
D B
DB
Junger
W G
WG
D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D006982:Hypertonic Solutions; D007165:Immunosuppression Therapy; D007249:Inflammation; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D015847:Interleukin-4 / Q000494:pharmacology*; D019169:Jurkat Cells; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000097:blood; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases
D006982:Hypertonic Solutions; D007376:Interleukin-2; D012462:Saline Solution, Hypertonic; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone