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Am J Physiol Cell Physiol (November 5, 2008). doi:10.1152/ajpcell.00447.2008
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Submitted on August 29, 2008
Revised on October 27, 2008
Accepted on November 4, 2008

Effect of Interleukin-15 on Depressed Splenic Dendritic Cell Functions Following Trauma-Hemorrhage

Takashi Kawasaki1, Mashkoor A Choudhry2, Martin G. Schwacha3, Kirby I. Bland3, and Irshad H. Chaudry4*

1 University of Alabama at Brimingham
2 Loyola University Chicago Medical Center
3 University of Alabama at Birmingham
4 U Alabama at Birmingham

* To whom correspondence should be addressed. E-mail: irshad.chaudry{at}ccc.uab.edu.

Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN (6-8 weeks) mice were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and ~90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4 x the shed blood volume in the form of Ringer's lactate). Two h later, mice were sacrificed, splenic DCs isolated and the effects of exogenous IL-15 on their co-stimulatory factors, MHC class II expression, ability to produce cytokines and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-{alpha}, IL-6 and IFN-{gamma} from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrates that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DCs. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-{gamma} production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H.







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