Gomez Christian R, Goral Joanna, Ramirez Luis, Kopf Manfred, Kovacs Elizabeth J
Department of Cell Biology, Neurobiology, and Anatomy, The Burn and Shock Trauma Institute, Alcohol Research Program, and Immunology and Aging Program, Loyola University Medical Center, Maywood, IL 60130, USA.
Shock. 2006 Jun;25(6):581-5. doi: 10.1097/01.shk.000029553.39081.ec.
This study was designed to determine whether the acute-phase response in aged mice is altered by interleukin (IL) 6 deficiency. Young and aged wild-type (WT) and IL-6 knockout (KO) BALB/C female mice were injected with lipopolysaccharide (LPS; 1.5 microg/g body weight). After 24 h, aged IL-6 KO mice had an improved survival when compared with aged WT mice. Serum levels of IL-6 in aged WT animals given LPS were determined and, as expected, were significantly higher when compared with young LPS-treated WT animals (P<0.05). Serum levels of the acute-phase protein, serum amyloid A, were 50% lower in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS (P<0.001). In contrast, the induction of LPS-binding protein was not affected by age or IL-6 deficiency in LPS-treated animals. Circulating levels of corticosterone were markedly reduced in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS. These data indicate that IL-6 is an important contributor to the outcome of the acute-phase response of aged individuals challenged with endotoxin. We conclude that the absence of IL-6, a cytokine that contributes to the elevated basal proinflammatory state observed in aging, can improve the ability of aged mice to withstand an otherwise lethal challenge of bacterial endotoxin.
本研究旨在确定白细胞介素（IL）-6缺乏是否会改变老年小鼠的急性期反应。将年轻和老年野生型（WT）及IL-6基因敲除（KO）的BALB/C雌性小鼠注射脂多糖（LPS；1.5微克/克体重）。24小时后，与老年WT小鼠相比，老年IL-6 KO小鼠的存活率有所提高。测定了给予LPS的老年WT动物血清中IL-6的水平，正如预期的那样，与年轻LPS处理的WT动物相比，其血清IL-6水平显著更高（P<0.05）。与给予LPS的老年WT小鼠相比，给予LPS的老年IL-6 KO小鼠急性期蛋白血清淀粉样蛋白A的血清水平降低了50%（P<0.001）。相比之下，LPS结合蛋白的诱导在LPS处理的动物中不受年龄或IL-6缺乏的影响。与给予LPS的老年WT小鼠相比，给予LPS的老年IL-6 KO小鼠循环中的皮质酮水平显著降低。这些数据表明，IL-6是老年个体对内毒素挑战的急性期反应结果的重要促成因素。我们得出结论，缺乏IL-6（一种导致在衰老过程中观察到基础促炎状态升高的细胞因子）可提高老年小鼠抵御原本致命的细菌内毒素挑战的能力。
