Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage

Kawasaki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH. Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage. Am J Physiol Cell Physiol 296: C124-C130, 2009. First published November 5, 2008; doi:10.1152/ajpcell.00447.2008.-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 mice (6-8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and similar to 90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4 x the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility 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 demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. 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.