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Targeting HMGB1 in the treatment of sepsis

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Abstract

Introduction: Sepsis refers to the host's deleterious and non-resolving systemic inflammatory response to microbial infections and represents the leading cause of death in the intensive care unit. The pathogenesis of sepsis is complex, but partly mediated by a newly identified alarmin molecule, the high mobility group box 1 (HMGB1).

Areas covered: Here we review the evidence that support extracellular HMGB1 as a late mediator of experimental sepsis with a wider therapeutic window and discuss the therapeutic potential of HMGB1-neutralizing antibodies and small molecule inhibitors (herbal components) in experimental sepsis.

Expert opinion: It will be important to evaluate the efficacy of HMGB1-targeting strategies for the clinical management of human sepsis in the future.

Acknowledgments

We are grateful to the peer reviewers for their critical and constructive comments.

Declaration of interest

Work in authors' laboratory was supported by grants from the National Center of Complementary and Alternative Medicine (NCCAM, R01AT005076) and the National Institute of General Medical Sciences (NIGMS, R01GM063075).

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