Novel insights for high mobility group box 1 protein-mediated cellular immune response in sepsis: A systemic review.

Background: High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinfl ammatory cytokine. In this article we reviewed briefl y the cellular immune response mediated by HMGB1 in infl ammation and sepsis.

Methods: This systemic review is mainly based on our own work and other related reports.

Results: HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity.

Conclusion: HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.