The cooperative effects of TNF‐α and IFN‐γ are determining factors in the ability of IL‐10 to protect mice from lethal endotoxemia
The cooperative effects of TNF‐α and IFN‐γ are determining factors in the ability of IL‐10 to protect mice from lethal endotoxemia
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TNF-α 和 IFN-γ 的协同作用是 IL-10 保护小鼠免受致命内毒素血症能力的决定因素
DOI：
10.1002/jlb.55.6.711
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发表时间：
1994
影响因子：
5.5
通讯作者：
J. Donkin
中科院分区：
文献类型：
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作者：
Sidney R. Smith;C. Terminelli;L. Kenworthy‐Bott;A. Calzetta;J. Donkin
最近的研究表明，白介素10(IL-10)具有保护小鼠免受内毒素致死作用的能力。在这项研究中，我们检测了IL-10对正常小鼠和短小棒状杆菌免疫小鼠对内毒素致死性的保护作用。在绝大多数实验中，重组小鼠IL-10(rMuIL-10)和重组人IL-10(rHuIL-10)在剂量达10μg/只时不能保护正常BALB/CJ小鼠免受内毒素诱导的死亡。尽管两种IL-10制剂都不能起到保护作用，但它们在预防致死剂量脂多糖引起的血清肿瘤坏死因子α(肿瘤坏死因子α)升高方面是非常有效的。此外，抗肿瘤坏死因子-α的中和抗体在单独给予BALB/CJ小鼠时仅起到部分保护作用。联合应用抗肿瘤坏死因子-α中和抗体和干扰素-7(干扰素-γ)可获得完全保护。与BALB/CJ小鼠相比，rMuIL-10和rHuIL-10均能保护正常BDF1小鼠免受致死性内毒素血症的影响，但IL-10虽能降低细小毛滴虫和正常BDF1小鼠血清中内毒素诱导的α反应，但对致死性内毒素血症无明显保护作用。抗肿瘤坏死因子-α和干扰素-γ的中和抗体在正常的BDF1小鼠中单独使用时具有保护作用，正如先前在微小弧菌免疫的小鼠中所证明的那样。这些结果表明，致死性内毒素血症是BALB/CJ和BDF1株正常小鼠以及微小弧菌免疫BDF1小鼠体内肿瘤坏死因子-α和干扰素-γ协同作用的结果。当干扰素-γ和肿瘤坏死因子-α之间的合作通过细胞因子的高水平产生而促进时，或者当有证据表明它们之间有很强的协同作用时，如在正常的BALB/CJ小鼠中，IL-10在保护小鼠免受致死性内毒素血症方面的效果似乎较差。J.Leukoc。比奥尔。55：711-718；1994。
Recent studies have demonstrated that interleukin‐10 (IL‐10) has the capacity to protect mice from the lethal effects of endotoxin. In this investigation, we have examined the ability of IL‐10 to protect both normal mice and Corynebacterium parvum‐primed mice against endotoxin lethality. In the overwhelming majority of experiments, recombinant murine IL‐10 (rMuIL‐10) and recombinant human IL‐10 (rHuIL‐10) did not protect normal BALB/cJ mice from lipopolysaccharide (LPS)‐induced lethality at doses up to 10 μg/mouse. Despite their inability to protect, both IL‐10 preparations were highly effective in preventing the increase in serum tumor necrosis factor α (TNF‐α) that occurred in response to the lethal dose of LPS. Moreover, a neutralizing antibody against TNF‐α gave only partial protection when administered alone to BALB/cJ mice. Treatment with a combination of neutralizing antibodies against TNF‐α and interferon‐7 (IFN‐γ) resulted in complete protection. In contrast to BALB/cJ mice, normal BDF1 mice were protected from lethal endotoxemia by treatment with both rMuIL‐10 and rHuIL‐10. However, IL‐10 did not protect C. parvum‐primed BDF1 against LPS lethality even though it caused a reduction in the LPS‐induced serum TNF‐α response in C. parvum‐primed mice as well as in normal BDF1 mice. Neutralizing antibodies against TNF‐α and IFN‐γ were protective when administered alone to normal BDF1 mice, as previously demonstrated in C. parvum‐primed mice. These findings suggest that lethal endotoxemia is a result of the cooperative activities of TNF‐α and IFN‐γ in normal mice of the BALB/cJ and BDF1 strains as well as in C. parvum‐primed BDF1 mice. IL‐10 appears to be less effective in protecting mice from lethal endotoxemia when cooperation between IFN‐γ and TNF‐α is facilitated by high‐level production of the cytokines as in C. parvum–primed mice or when there is evidence of strong synergy between them as in normal BALB/cJ mice. J. Leukoc. Biol. 55: 711–718; 1994.
影响因子：
4.4
作者：
K. Sheehan;N. Ruddle;R. Schreiber
通讯作者：
K. Sheehan;N. Ruddle;R. Schreiber
影响因子：
4.4
作者：
R. Schreiber;L. Hicks;A. Celada;N. Buchmeier;P. Gray
通讯作者：
R. Schreiber;L. Hicks;A. Celada;N. Buchmeier;P. Gray
鼠 IL-1 α 单克隆抗体。
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fuhlbrigge,RC;Sheehan,KC;Schreiber,RD;Chaplin,DD;Unanue,ER
通讯作者：
Unanue,ER