Critical role of CD14 for production of proinflammatory cytokines and cytokine inhibitors during sepsis with failure to alter morbidity or mortality
Critical role of CD14 for production of proinflammatory cytokines and cytokine inhibitors during sepsis with failure to alter morbidity or mortality
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DOI：
10.1128/iai.69.4.2099-2106.2001
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发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
Remick, DG
中科院分区：
文献类型：
--
作者：
Ebong, SJ;Goyert, SM;Remick, DG
我们研究了CD 4缺陷（CD 14敲除[CD 14 KO]）小鼠盲肠结扎穿孔（CLP）诱导脓毒症期间的免疫病理生理反应。我们的研究旨在专门测试CD 14在脓毒症炎症反应中的作用，并确定改变是否会改善发病率或死亡率。使用CLP模型并使用适当的抗生素治疗诱导脓毒症。随着穿刺尺寸的增加（18号[18 G]、21 G和25 G），CD 14 KO小鼠中脓毒症的严重程度增加。CLP后，假手术组和25 G CLP组的体温（12 h）和粗大运动活动水平恢复正常，而21 G和18 G CLP组表现出严重的体温过低，伴有粗大运动活动和体重下降。在21 G CLP后，CD 14 KO和对照小鼠之间的存活率、体温、体重或活动水平没有显著差异。然而，CD 14 KO小鼠在21 G CLP后血液中表达的促炎性（白细胞介素-1 β [IL-1 β]、肿瘤坏死因子[TNF]和IL-6）和TNF（IL-10、IL-1受体拮抗剂和TNF受体I和II）细胞因子减少2 - 4倍。在CD 14 KO小鼠中，趋化因子巨噬细胞炎性蛋白2 α和KC的血浆水平也类似地降低。在CD 14 KO小鼠的腹腔中观察到细胞因子和细胞因子抑制剂水平降低的类似趋势。我们的研究结果表明，CD 14活化途径在促炎细胞因子和细胞因子抑制剂的产生中起着关键作用，但对CLP脓毒症模型诱导的发病率或死亡率的影响很小。
We investigated the immunopathophysiologic responses during sepsis induced by cecal ligation and puncture (CLP) in CD4-deficient (CD14 knockout [CD14KO]) mice. Our studies were designed to specifically test the role of CD14 in the inflammatory response to sepsis and to ascertain if alterations would improve morbidity or mortality. Sepsis was induced using the CLP model with appropriate antibiotic treatment. The severity of sepsis increased in the CD14KO mice with increasing puncture size (18 gauge [18G], 21G, and 25G). Following CLP, body temperature (at 12 h) and gross motor activity levels of the sham and 25G CLP groups recovered to normal, while the 21G and 18G CLP groups exhibited severe hypothermia coupled with decreased gross motor activity and body weight. There were no significant differences in survival, temperature, body weight, or activity levels between CD14KO and control mice after 21G CLP. However, CD14KO mice expressed two- to fourfold less pro-inflammatory (interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF], and IL-6) and antiinflammatory (IL-10, IL-1 receptor antagonist, and TNF receptors I and II) cytokines in the blood after 21G CLP. Plasma levels of the chemokines macrophage inflammatory protein 2 alpha and KC were similarly reduced in CD14KO mice. A similar trend of decreased cytokine and cytokine inhibitor levels was observed in the peritoneal cavity of CD14KO mice. Our results indicate that the CD14 pathway of activation plays a critical role in the production of both pro inflammatory cytokines and cytokine inhibitors but has minimal impact on the morbidity or mortality induced by the CLP model of sepsis.