IL-23 neutralization protects mice from Gram-negative endotoxic shock
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- 作者：Maria Laura Belladonna ; Carmine Vacca ; Claudia Volpi ; Antonio Giampietri ; Maria Cristina Fioretti ; Paolo Puccetti ; Ursula Grohmann and Franca Campanile
- 关键词：IL-23 ; Gram-negative sepsis ; Endotoxin shock ; Anti-p19
- 刊名：Cytokine
- 出版年：2006
- 出版时间：21 May 2006
- 年：2006
- 卷：34
- 期：3-4
- 页码：161-169
- 全文大小：259 K
文摘
Excessive production of proinflammatory cytokines, including TNF-α, IL-1, IL-6, IL-12, and IFN-γ is thought to contribute significantly to lethality in septic shock syndromes. IL-23 is a heterodimeric cytokine that combines the p40 subunit of IL-12 with a specific p19 subunit. Similar to IL-12, IL-23 is considered to be a key immunoregulator in the response to pathogenic organisms but its contribution to Gram-negative endotoxic shock is as yet unclear. Using an established shock model with Pseudomonas aeruginosa, we found early and sustained expression of IL-23 p19 transcripts in the spleens of mice undergoing lethal challenge with the bacterium. Administration of p19-neutralizing antibody reduced mortality in a dose-dependent fashion. Survival in P. aeruginosa-challenged mice was associated with a dramatic decrease in circulating levels of the pathogenetic cytokines, TNF-α and IFN-γ. Hence, IL-23 may represent a new therapeutic target in Gram-negative endotoxic shock.