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首页> 外文期刊>Infection and immunity >Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection.
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Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection.

机译：B组链球菌感染的新生大鼠模型中细胞因子的出现和抗肿瘤坏死因子α抗体的作用。

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Cytokines are suspected of playing an important role in the pathophysiology of septic shock. This study was undertaken to determine whether tumor necrosis factor alpha (TNF-alpha) induces the production of other cytokines and mediates mortality in a neonatal rat model of sepsis caused by group B streptococci (GBS). We have measured TNF-alpha, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) levels in neonatal rats infected with different strains (H738, 259, and 90) and doses (1 50% lethal dose [LD50] and 5 90% lethal doses [LD90]) of type III GBS. TNF-alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial plasma samples. IL-1 alpha and IFN-gamma were measured in spleen homogenates by enzyme-linked immunosorbent assay kits by using antibodies raised against the corresponding mouse cytokines. Plasma TNF-alpha levels significantly rose above baseline values within 12 h after intraperitoneal challenge with 5 LD90 of GBS strain H738, corresponding to 3 x 10(3) CFU. A mean peak TNF-alpha concentration of 232 +/- 124 U/ml was reached at 20 h. Peak IL-1 alpha and IL-6 levels of 766 +/- 404 U/g and 1,033 +/- 520 U/ml, respectively, were reached at 24 h after bacterial challenge. Maximal spleen concentrations of IFN-gamma (449 +/- 283 U/g) were measured at 36 h. Concentrations of TNF-alpha, but not other cytokines, remained significantly elevated at 72 h, a time when mortality approached 100%. Significant correlations were found between concentrations of each of the cytokines tested and the logs of CFU concentrations in the blood. In order to ascertain whether TNF-alpha influenced the production of other cytokines, rat pups received two injections of anti-murine TNF-alpha or normal rabbit serum at 2 h before and at 26 h after challenge with live GBS. Plasma TNF-alpha bioactivity was undetectable in anti-TNF-alpha-treated animals, while IL-6 and IFN-gamma, but not IL-1 alpha, levels were significantly reduced, compared with normal serum controls. Rat pups pretreated with anti-TNF-alpha serum and infected with 1 and 5 LD90 of strains H738 and 259 showed enhanced early (48 to 72 h) survival. However, by 96 h this protection was no longer apparent.
机译：怀疑细胞因子在败血性休克的病理生理中起重要作用。进行这项研究来确定在B组链球菌（GBS）引起的脓毒症新生鼠模型中，肿瘤坏死因子α（TNF-alpha）是否诱导其他细胞因子的产生并介导死亡率。我们已经测量了感染了不同菌株（H738、259和90）的新生大鼠中的TNF-alpha，白介素1 alpha（IL-1 alpha），白介素6（IL-6）和γ干扰素（IFN-γ）水平）和III型GBS的剂量（1个50％致死剂量[LD50]和5个90％致死剂量[LD90]）。在系列血浆样品中分别通过L929细胞毒性和B9增殖测定法检测到TNF-α和IL-6。通过使用针对相应小鼠细胞因子的抗体，通过酶联免疫吸附测定试剂盒在脾匀浆中测量IL-1α和IFN-γ。在腹腔内用5 LD90的GBS菌株H738攻击腹腔后12小时内，血浆TNF-α水平显着升高至基线以上，相当于3 x 10（3）CFU。在20 h时，TNF-α的平均峰值浓度达到232 +/- 124 U / ml。在细菌攻击后24小时，分别达到766 +/- 404 U / g和1,033 +/- 520U / ml的IL-1α和IL-6峰值水平。在36小时时测量最大脾脏中IFN-γ的浓度（449 +/- 283U / g）。死亡率达到100％时，在72小时时，TNF-α的浓度（而非其他细胞因子）仍显着升高。发现每种被测细胞因子的浓度与血液中CFU浓度的对数之间存在显着的相关性。为了确定TNF-α是否影响其他细胞因子的产生，在用活GBS攻击前2小时和攻击后26小时，大鼠幼鼠两次注射抗鼠TNF-α或正常兔血清。在抗TNF-α治疗的动物中，血浆TNF-α的生物活性无法检测到，而与正常血清对照组相比，IL-6和IFN-γ的水平却大大降低，但IL-1α却没有。用抗TNF-α血清预处理并感染1和5 LD90菌株H738和259的大鼠幼仔显示出增强的早期存活（48至72小时）。但是，到96小时，这种保护不再明显。

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