失血性休克小鼠模型中免疫功能的年龄和性别相关差异：白细胞介素-10可恢复老年雌性小鼠的免疫抑制而不降低死亡率。

Age- and gender-related differences of the immune function in a murine model of hemorrhagic shock: IL-10 restores immunodepression in aged females without reduction of mortality.

作者信息

Mees Soeren Torge, Dohm Christoph, Broetzmann Kerstin, Schroeder Joerg, Faendrich Fred, Kremer Bernd, Kahlke Volker

机构信息

Department of General Surgery, University of Muenster, Waldeyerstr. 1, 48147, Muenster, Germany.

出版信息

Langenbecks Arch Surg. 2007 Sep;392(5):629-38. doi: 10.1007/s00423-007-0152-y. Epub 2007 Mar 2.

DOI:10.1007/s00423-007-0152-y

PMID:17334776

Abstract

INTRODUCTION

Interleukin-10 (IL-10) treatment has been shown to have beneficial effects on the immune function after hemorrhagic shock and to improve survival after subsequent sepsis in young male mice, but not in young females. Although it was demonstrated that the immune function under these conditions is reversed with age, it remains unclear whether the observed gender-related effect of IL-10 treatment continues to exist in aged mice.

MATERIALS AND METHODS

Aged male and female CBA/J mice (18-19 months) were subjected to hemorrhage (35 +/- 5 mmHg for 90 min) or sham operation. At resuscitation, each received either 10-microg recombinant murine (rm)IL-10 or placebo i.p. At 48 h after resuscitation, either the mice were killed and the plasma, splenic macrophages (sM phi), and splenocytes were harvested or polymicrobial sepsis was induced by cecal ligation and puncture (CLP). After CLP, either survival over 10 days was determined or, 4 h after CLP, tissues were again harvested and cytokine-released in vitro were assessed by enzyme-linked immunosorbent assay.

RESULTS

Early IL-10 treatment restored depressed proinflammatory immune response (TNF-alpha, IL-1 beta) and Th1 response of splenocytes in aged females after hemorrhage, whereas having no effects or having suppressive effects in aged males. Subsequent sepsis combined with placebo treatment led to a significant suppression of proinflammatory cytokine release of sM phi and a significant increase of Th2 response in both males and females associated with high mortality (80-100%, respectively) after CLP. These effects were not influenced by early rmIL-10 treatment.

CONCLUSION

After hemorrhage, early rmIL-10 treatment restored immune function in aged females, but not in males. However, in contrast to young mice, rmIL-10 treatment had no effect on survival and immune function after CLP in aged mice.

摘要

引言

白介素-10（IL-10）治疗已被证明对失血性休克后的免疫功能具有有益作用，并能提高年轻雄性小鼠随后发生脓毒症后的生存率，但对年轻雌性小鼠无效。尽管已证明这些条件下的免疫功能会随着年龄的增长而逆转，但尚不清楚观察到的IL-10治疗的性别相关效应在老年小鼠中是否仍然存在。

材料与方法

将老年雄性和雌性CBA/J小鼠（18 - 19个月）进行出血处理（35±5 mmHg，持续90分钟）或假手术。复苏时，每只小鼠腹腔注射10微克重组鼠（rm）IL-10或安慰剂。复苏后48小时，处死小鼠并收集血浆、脾巨噬细胞（sM phi）和脾细胞，或者通过盲肠结扎和穿刺（CLP）诱导多微生物脓毒症。CLP后，确定10天内的生存率，或者在CLP后4小时再次收集组织，并通过酶联免疫吸附测定评估体外释放的细胞因子。

结果

早期IL-10治疗可恢复老年雌性小鼠出血后脾细胞中受抑制的促炎免疫反应（TNF-α、IL-1β）和Th1反应，而对老年雄性小鼠无影响或有抑制作用。随后的脓毒症联合安慰剂治疗导致sM phi促炎细胞因子释放显著受抑制，且雄性和雌性小鼠的Th2反应均显著增加，CLP后死亡率较高（分别为80 - 100%）。这些效应不受早期rmIL-10治疗的影响。