Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?

Sepsis refers to a systemic inflammatory response syndrome resulting from microbial infections, and is partly attributable to dysregulated inflammation and associated immunosuppression. A ubiquitous nuclear protein, HMGB1, is secreted by activated leukocytes to orchestrate inflammatory responses during early stages of sepsis. When it is released by injured somatic cells at overwhelmingly higher quantities, HMGB1 may induce macrophage pyroptosis and immunosuppression, thereby impairing the host’s ability to eradicate microbial infections. A number of endogenous proteins have been shown to bind HMGB1 to modulate its extracellular functions. Here, we discuss an emerging possibility to develop therapeutic antibodies against harmless proteins that collude with pathogenic mediators for the clinical management of human sepsis and other inflammatory diseases.