Moss N M, Gough D B, Jordan A L, Grbic J T, Wood J J, Rodrick M L, Mannick J A
Department of Surgery, Harvard Medical School, Boston, MA 02115.
Surgery. 1988 Nov;104(5):882-7.
Suppression of cellular immunity and increased susceptibility to sepsis frequently accompany thermal injury. However, a convincing association between the two has been difficult to establish in human beings. Therefore we chose to investigate the relationship of impaired cell-mediated immunity with susceptibility to sepsis in an animal model. We studied the response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production by splenocytes from mice subjected to a standard 25% scald burn and killed at intervals of 3, 5, 7, 10, 14, and 25 days after thermal injury. Burned mice were compared in all instances to sham-burn animals (i.e., animals that had been anesthetized and shaved but not burned). We also studied mortality after cecal ligation and puncture (CLP), as a septic challenge, in burned and control animals at the same postburn intervals. We found maximal suppression (50% to 55%) of the PHA response at 10 to 14 days after injury and maximum suppression (68%) of IL-2 production at 7 days. Both of these parameters returned to normal by postinjury day 28. Mortality after CLP increased gradually from control levels after thermal injury up to a maximum of 88% on postburn day 10 and also returned to control levels after 28 days after burn. Significant correlations were found between mortality after CLP in the postburn period and suppression of the PHA response, on the one hand, and the suppression of IL-2 production, on the other (r = 0.89 and 0.91, respectively; p less than 0.05). This result implies a causal relationship between impaired cell-mediated immunity and susceptibility to sepsis after burn injury.
细胞免疫抑制和脓毒症易感性增加常伴随热损伤。然而，在人类中很难确定两者之间令人信服的关联。因此，我们选择在动物模型中研究细胞介导的免疫受损与脓毒症易感性之间的关系。我们研究了标准25%烫伤小鼠的脾细胞对植物血凝素（PHA）的反应以及白细胞介素-2（IL-2）的产生，并在热损伤后的3、5、7、10、14和25天间隔处死小鼠。在所有情况下，将烧伤小鼠与假烧伤动物（即已麻醉和剃毛但未烧伤的动物）进行比较。我们还研究了在相同烧伤后间隔时间，烧伤和对照动物在盲肠结扎和穿刺（CLP）作为脓毒症挑战后的死亡率。我们发现，损伤后10至14天PHA反应受到最大抑制（50%至55%），7天时IL-2产生受到最大抑制（68%）。这两个参数在损伤后第28天恢复正常。CLP后的死亡率从热损伤后的对照水平逐渐增加，在烧伤后第10天最高达到88%，并且在烧伤后28天也恢复到对照水平。一方面，在烧伤后期间CLP后的死亡率与PHA反应的抑制之间，另一方面与IL-2产生的抑制之间发现了显著相关性（r分别为0.89和0.91；p小于0.05）。这一结果意味着烧伤后细胞介导的免疫受损与脓毒症易感性之间存在因果关系。
