Interleukin-12 treatment restores normal resistance to bacterial challenge after burn injury.
Interleukin-12 treatment restores normal resistance to bacterial challenge after burn injury.
复制标题
Interleukin-12 治疗可恢复烧伤后对细菌攻击的正常抵抗力。
DOI：
10.1016/s0039-6060(96)80300-x
复制
发表时间：
1996
期刊：
影响因子：
3.8
通讯作者：
Rodrick,ML
中科院分区：
文献类型：
--
作者：
O'Suilleabhain,C;O'Sullivan,ST;Kelly,JL;Lederer,J;Mannick,JA;Rodrick,ML
本实验室的初步研究表明，在烧伤动物模型中，用白细胞介素-12（IL-12）（一种诱导T辅助细胞-1淋巴细胞表型表达的细胞因子）治疗可增加脓毒症后的存活率。本研究的目的是确定IL-12治疗的疗效，并探讨其mechanisms of action.MethodsAdult雄性A/J小鼠进行25%全层烧伤或假烧伤。从烧伤后第3天开始，各组小鼠每天接受5次IL-12、干扰素-γ（IFN-γ）或盐水溶液注射。部分动物接受抗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），并观察存活情况。一些动物被杀死在第10天，和CD 4-富集脾细胞刺激抗-CD 3抗体或刀豆球蛋白A和研究细胞因子的产生和mRNA expression. ResultsIL-12治疗，25 ng每天5天，增加生存的烧伤组CLP后的假烧伤对照组。在IL-12治疗前1天给予抗IFN-γ抗体500 μg，降低IL-12的功效。IFN-γ治疗，7000单位，中度增加生存。IL-12对假烧伤组的存活率没有影响。IL-12治疗可使CLP时CD 4+淋巴细胞IL-4水平明显降低，IFN-γ水平和mRNA表达水平中度升高，而对IL-2无影响。结论IL-12是目前为止治疗烧伤合并CLP的最有效的药物。它至少部分通过IFN-γ发挥作用。然而，IFN-γ治疗不如IL-12有效。
BackgroundPreliminary 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.MethodsAdult 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-γ (IFN-γ), or saline solution. Some animals received anti-IFN-γ 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.ResultIL-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-γ antibody, 500 μg, administered 1 day before IL-12 treatment, reduced the efficacy of IL-12. IFN-γ 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-γ production and mRNA expression without affecting IL-2.ConclusionsIL-12 is the most effective therapy so far tested in this burn plus CLP model. It acts at least in part through IFN-γ. However, IFN-γ therapy was not as effective IL-12.