Mack V E, McCarter M D, Naama H A, Calvano S E, Daly J M
Department of Surgery, New York Hospital-Cornell, University Medical College, New York 10021, USA.
J Surg Res. 1997 May;69(2):399-407. doi: 10.1006/jsre.1997.5093.
Following trauma, there is an increase of Th2 cytokines (IL-4, IL-6, and IL-10) and a decrease in Th1 cytokines (IFN-gamma and IL-2) that may account for impaired cellular immunity. However, the functional significance of a dominant Th2 pattern to the host remains unclear. The aim of this study was to evaluate whether Candida albicans (CA) sepsis in the setting of a Th2 response to trauma leads to increased mortality and to examine the mediators involved. Female BALB/c mice were randomized (12 per group) to receive no injury (C); trauma, consisting of a combined femur fracture and 40% total blood loss (T); no injury plus CA infection (C+CA); and CA infection 1 week following trauma (T+CA). Survival was then followed for 3 weeks. In a separate study, mice were treated as above (5 per group) and sacrificed. Harvested splenocytes were evaluated for concanavalin A-stimulated cytokine production and liver and kidney homogenates were plated to evaluate CA growth per organ and examined histologically. Candida infection at 1 week following trauma resulted in significantly increased mortality compared to infected controls. Furthermore, the Th2 dominant cytokine pattern was significantly augmented in the presence of CA infection in both C+CA and T+CA groups. Additional analysis showed significant growth of CA in liver and kidney homogenates from T+CA compared to C+CA mice. These results suggest that injured and infected mice demonstrate augmentation of Th2 dominant responses above that of injury or infection alone, as well as a decreased ability to clear Candida which may partially explain the increase in mortality observed. Therapies designed to neutralize Th2 cytokines or augment Th1 cytokines may prove beneficial in the setting of sepsis following trauma.
创伤后，Th2细胞因子（IL-4、IL-6和IL-10）增加，Th1细胞因子（IFN-γ和IL-2）减少，这可能导致细胞免疫受损。然而，Th2主导模式对宿主的功能意义仍不清楚。本研究的目的是评估在创伤后Th2反应背景下白色念珠菌（CA）败血症是否会导致死亡率增加，并研究其中涉及的介质。将雌性BALB/c小鼠随机分组（每组12只），分别接受无损伤（C）；创伤（包括股骨骨折合并40%总失血量，T）；无损伤加CA感染（C+CA）；以及创伤后1周的CA感染（T+CA）。然后观察3周的生存率。在另一项研究中，小鼠按上述方法处理（每组5只）后处死。评估收获的脾细胞对刀豆蛋白A刺激的细胞因子产生情况，并将肝和肾匀浆接种以评估每个器官的CA生长情况，并进行组织学检查。与感染对照组相比，创伤后1周的念珠菌感染导致死亡率显著增加。此外，在C+CA和T+CA组中，CA感染均显著增强了Th2主导的细胞因子模式。进一步分析表明，与C+CA小鼠相比，T+CA组肝和肾匀浆中的CA生长显著。这些结果表明，受伤且感染的小鼠Th2主导反应增强，超过单独损伤或感染，且清除念珠菌的能力下降，这可能部分解释了观察到的死亡率增加。旨在中和Th2细胞因子或增强Th1细胞因子的疗法可能对创伤后败血症有益。
