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用同源二聚体白细胞介素-12(IL-12)p40进行治疗可保护小鼠免受IL-12依赖性休克,但不能使其免受肿瘤坏死因子α依赖性休克。

Treatment with homodimeric interleukin-12 (IL-12) p40 protects mice from IL-12-dependent shock but not from tumor necrosis factor alpha-dependent shock.

作者信息

Mattner F, Ozmen L, Podlaski F J, Wilkinson V L, Presky D H, Gately M K, Alber G

机构信息

Department of Infectious Diseases, F. Hoffmann-La Roche AG, Basel, Switzerland.

出版信息

Infect Immun. 1997 Nov;65(11):4734-7. doi: 10.1128/iai.65.11.4734-4737.1997.

Abstract

The role of interleukin-12 (IL-12) was investigated in different shock models using anti-IL-12 reagents. IL-12 is composed of two disulfide-bonded subunits, p35 and p40. The IL-12 p40 homodimer (p40)2 has been shown to be a potent IL-12 antagonist in vitro. We investigated its in vivo inhibitory capacity in different shock models of mice. We could demonstrate that (p40)2 is able to protect mice from septic shock in primarily IL-12-dependent models such as the Shwartzman reaction and lipopolysaccharide (LPS)-induced shock, whereas (p40)2 has no effect in the tumor necrosis factor alpha-dependent LPS/D-GalN shock model. In IL-12-dependent shock models, (p40)2 inhibits IL-12-induced gamma interferon production and thereby interferes with the cascade of cytokine release, finally leading to death.

摘要

使用抗白细胞介素-12(IL-12)试剂,在不同的休克模型中研究了IL-12的作用。IL-12由两个通过二硫键结合的亚基p35和p40组成。IL-12 p40同二聚体(p40)2在体外已被证明是一种有效的IL-12拮抗剂。我们在小鼠的不同休克模型中研究了其体内抑制能力。我们能够证明,在主要依赖IL-12的模型如施瓦茨曼反应和脂多糖(LPS)诱导的休克中,(p40)2能够保护小鼠免受脓毒性休克,而在肿瘤坏死因子α依赖性LPS/D-半乳糖胺休克模型中,(p40)2没有作用。在依赖IL-12的休克模型中,(p40)2抑制IL-12诱导的γ干扰素产生,从而干扰细胞因子释放级联反应,最终导致死亡。

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