O'Suilleabhain C, O'Sullivan S T, Kelly J L, Lederer J, Mannick J A, Rodrick M L
Department of Surgery, Harvard Medical School/Brigham and Women's Hospital, Boston, Mass. 02115, USA.
Surgery. 1996 Aug;120(2):290-6. doi: 10.1016/s0039-6060(96)80300-x.
Preliminary studies in this laboratory have shown that treatment with interleukin-12 (IL-12), a cytokine that induces expression of the T-helper-1 lymphocyte phenotype, in an animal model of burn injury increased survival after a septic challenge. The purpose of this study was to define the efficacy of IL-12 therapy and to explore its mechanism of action.
Adult male A/J mice were subjected to 25% full-thickness scald or sham burn. Starting on day 3 after burn, groups of mice received five daily injections of IL-12, interferon-gamma (IFN-gamma), or saline solution. Some animals received anti-IFN-gamma monoclonal antibody. At day 10 most animals underwent cecal ligation and puncture (CLP) and were observed for survival. Some animals were killed at day 10, and CD4-enriched splenocytes were stimulated with anti-CD3 antibody or concanavalin A and were studied for cytokine production and mRNA expression.
IL-12 treatment, 25 ng daily for 5 days, increased survival of the burn group after CLP to that of the sham burn control group. Anti-IFN-gamma antibody, 500 micrograms, administered 1 day before IL-12 treatment, reduced the efficacy of IL-12. IFN-gamma treatment, 7000 units, moderately increased survival. IL-12 had no effect on survival of the sham burn group. At the time of CLP IL-12 therapy had induced a marked decrease in CD4+ lymphocyte IL-4 and a moderate increase in IFN-gamma production and mRNA expression without affecting IL-2.
IL-12 is the most effective therapy so far tested in this burn plus CLP model. It acts at least in part through IFN-gamma. However, IFN-gamma therapy was not as effective as IL-12.
本实验室的初步研究表明，在烧伤损伤动物模型中，用白细胞介素-12（IL-12，一种诱导辅助性T1淋巴细胞表型表达的细胞因子）进行治疗可提高脓毒症激发后的生存率。本研究的目的是确定IL-12治疗的疗效并探索其作用机制。
成年雄性A/J小鼠接受25%全层烫伤或假烧伤。从烧伤后第3天开始，每组小鼠每日接受5次IL-12、干扰素-γ（IFN-γ）或盐溶液注射。一些动物接受抗IFN-γ单克隆抗体。在第10天，大多数动物接受盲肠结扎和穿刺（CLP）并观察生存率。一些动物在第10天处死，用抗CD3抗体或刀豆蛋白A刺激富含CD4的脾细胞，并研究细胞因子产生和mRNA表达。
每天25 ng，连续5天的IL-12治疗使CLP后烧伤组的生存率提高到假烧伤对照组的水平。在IL-12治疗前1天给予500 μg抗IFN-γ抗体可降低IL-12的疗效。7000单位的IFN-γ治疗可适度提高生存率。IL-12对假烧伤组的生存率无影响。在CLP时，IL-12治疗导致CD4+淋巴细胞IL-4显著减少，IFN-γ产生和mRNA表达适度增加，而不影响IL-2。
在这个烧伤加CLP模型中，IL-12是迄今为止测试的最有效的治疗方法。它至少部分通过IFN-γ起作用。然而，IFN-γ治疗不如IL-12有效。
