Differences in cytokine response and induction of nitric oxide synthase in endotoxin-resistant and endotoxin-sensitive mice after intravenous gram-negative infection.
Differences in cytokine response and induction of nitric oxide synthase in endotoxin-resistant and endotoxin-sensitive mice after intravenous gram-negative infection.
复制标题
内毒素抵抗型和内毒素敏感型小鼠静脉注射革兰氏阴性菌后细胞因子反应和一氧化氮合酶诱导的差异。
作者：
T. Evans;Eddy Strivens;A. Carpenter;J. Cohen
先前的报道表明，内毒素耐药的小鼠C3H/HeJ菌株比内毒素敏感的亲本菌株C3H/HeN更容易感染，尽管它们从未在脓毒症的静脉注射模型中进行比较。因此，我们将这些小鼠品系用于革兰氏阴性脓毒症的静脉注射模型，比较它们对感染的敏感性、细胞因子反应和肝脏中一氧化氮合酶的诱导水平。通过静脉感染大肠杆菌，我们发现尽管C3H/HeJ小鼠的tnf - α反应明显减弱，但这两种菌株对该生物体的敏感性大致相同。两株感染后ifn - γ水平相同；C3H/HeJ组小鼠肝脏中诱导的一氧化氮合酶水平大约是C3H/HeJ组小鼠的四倍。这种差异不能用细菌负荷的差异来解释。这些实验表明，除tnf - α以外的其他因素在决定革兰氏阴性脓毒症的预后方面也很重要，并且tnf - α不是体内感染后诱导肝一氧化氮合酶的主要因素。
Previous reports have suggested that the endotoxin-resistant C3H/HeJ strain of mouse is more susceptible to infection than is the endotoxin-sensitive parent strain, C3H/HeN, although they have never been compared in an i.v. model of sepsis. We therefore have used these mouse strains in an i.v. model of Gram-negative sepsis to compare their sensitivities to infection, their cytokine responses, and the levels of induction of the enzyme nitric oxide synthase assayed in their livers. By using i.v. infection with Escherichia coli we have found that both strains are approximately equally sensitive to this organism, despite the C3H/HeJ mice having a markedly attenuated TNF-alpha response. IFN-gamma levels after infection were identical in the two strains; the levels of nitric oxide synthase induced in their livers were about fourfold greater in the C3H/HeJ mice. This difference could not be explained by differences in bacterial load. These experiments suggest that factors other than TNF-alpha are important in determining outcome from Gram-negative sepsis and that TNF-alpha is not a major factor in the induction of hepatic nitric oxide synthase after infection in vivo.