Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis.

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Yang M, Cao L, Xie M, Yu Y, Kang R, Yang L, Zhao M, Tang D

Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis.

Biochem Pharmacol. 2013 Aug 1;86(3):410-8. doi: 10.1016/j.bcp.2013.05.013. Epub 2013 May 22.

PubMed ID

23707973 [ View in PubMed

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Abstract

Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities. As an inhibitor of autophagy, chloroquine specifically inhibited HMGB1-induced Ikappa-B degradation and NF-kappaB activation. These findings define a novel mechanism for the anti-inflammatory effects of chloroquine and also suggest a new potential clinical use for this drug in the setting of sepsis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Chloroquine	High mobility group protein B1	Protein	Humans	Unknown	Inhibitor	Details