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

机译:白细胞介素15对创伤性出血后脾脏树突状细胞功能下降的影响

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摘要

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 ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× 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-α, IL-6, and IFN-γ 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-γ 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.
机译:尽管创伤性出血(T-H)诱导了脾脏树突状细胞(DC)的成熟和抗原呈递能力的提高,但仍不清楚IL-15是否调节脾脏DC功能。因此,本研究的目的是研究IL-15对T-H后脾脏DC功能的影响。将C3H / HeN雄性小鼠(6-8周大)随机分配为T-H或假手术。 T-H由中线剖腹术和约90分钟的出血性休克(血压35 mmHg)诱导,然后进行液体复苏(4倍于乳酸林格氏液的排出血量)。两个小时后,杀死小鼠,分离脾脏DC,并测量外源IL-15对其共刺激因子,主要组织相容性II类表达,产生细胞因子的能力和抗原呈递的影响。结果表明,脾脏DC的IL-15生产能力在T-H后降低。离体暴露于IL-15会减弱T-H后脾脏DC产生的TNF-α,IL-6和IFN-γ的抑制作用。此外,表面抗原的表达研究表明外源性IL-15减弱了T-H诱导的DC激活下调。 IL-15治疗也减弱了T-H后脾脏DC抗原呈递功能的抑制。此外,IL-15通过脾脏DC增强IL-12诱导的IFN-γ产生和抗原呈递。这些数据表明,在T-H后用IL-15进行离体治疗可对脾脏DC产生有益作用。脾脏DC抑制IL-15产生可能导致宿主对T-H感染的敏感性增加。

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