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Published on: May 2, 2018
IL-23 neutralization protects mice from Gram-negative endotoxic shock
Maria Laura Belladonna1, Carmine Vacca, Claudia Volpi
1Department of Experimental Medicine and Biochemical Sciences, Section of Pharmacology, University of Perugia, Via del Giochetto, Perugia 06126, Italy. laurabell@tin.it
Cytokine
|June 9, 2006
Summary
Interleukin-23 (IL-23) plays a role in lethal Gram-negative endotoxic shock. Neutralizing IL-23 reduced mortality and levels of harmful cytokines in a mouse model.
Area of Science:
- Immunology
- Pathophysiology
- Microbiology
Background:
- Proinflammatory cytokines like TNF-alpha contribute to septic shock lethality.
- Interleukin-23 (IL-23), a cytokine related to IL-12, is an immunoregulator whose role in Gram-negative endotoxic shock is not well understood.
Purpose of the Study:
- To investigate the role of IL-23 in a mouse model of Gram-negative endotoxic shock caused by Pseudomonas aeruginosa.
- To determine if IL-23 could be a therapeutic target for this condition.
Main Methods:
- Establishment of a Pseudomonas aeruginosa-induced septic shock model in mice.
- Monitoring of IL-23 p19 transcript expression in spleen tissue.
- Administration of p19-neutralizing antibody to assess its effect on mortality and cytokine levels.
Main Results:
- Early and sustained expression of IL-23 p19 transcripts was observed in mice challenged with P. aeruginosa.
- Treatment with p19-neutralizing antibody significantly reduced mortality in a dose-dependent manner.
- Survival was correlated with decreased circulating levels of TNF-alpha and IFN-gamma.
Conclusions:
- IL-23 is implicated in the pathogenesis of Gram-negative endotoxic shock.
- Neutralizing IL-23 offers a potential therapeutic strategy for reducing mortality in septic shock.
- IL-23 represents a novel therapeutic target for Gram-negative endotoxic shock.
