Sepsis Treatment: HMGB1

High-Mobility Group Box-1 (HMGB1) protein is a type of cellular protein that was discovered 30 years ago. The protein was originally found as a type of histone meaning it serves as a nuclear binding protein, facilitating the transcription of genes from DNA to mRNA. HMGB1 was also found to be involved in the recombination and repair of DNA.

In recent years, it was discovered that these proteins are also involved in inflammation. This role in inflammation is because HMGB1 is a pro-inflammatory cytokine, molecules that stimulate proinflammatory responses. This protein is produced during systemic inflammation which is when the immune system is constantly fighting against foreign invaders and is characteristic of sepsis. Since levels of HMGB1 are elevated in many conditions of sepsis, this protein can serve as a good biomarker for the disease as well as a target for various treatments.

While the main source of HMGB1 is cell death, there are many types of cell death. Necrosis is the death of cells due to disease, injury, or failure of the blood supply. Apoptosis is the death of cells as part of normal growth and development. Pyroptosis is the death of cells triggered by inflammation. The different types of cell death induce the release of different forms of HMGB1. These different forms are known as isoforms. Therefore, to understand HMGB1, studies have examined the various isoforms of HMGB1 and its impact on inflammatory responses of the body. Scientists have also tried to use knowledge of HMGB1 to treat sepsis by hypothesizing that the blockade of HMGB1 proteins can aid in rescue from lethal sepsis.

As research continues to further our understanding of HGMB1 and ways to properly regulate its release, it may be a promising focus for many future sepsis treatments.