HMGB1 as a drug target in staphylococcal pneumonia.

High mobility group box (HMGB)1 is a small DNA-binding protein. In the nucleus, HMGB1 plays a role in gene expression and DNA replication. When it is released or secreted into the extracellular milieu, HMGB1 functions as a pro-inflammatory cytokine-like mediator. Recently reported data support the view that treatment with a neutralizing anti-HMGB1 antibody ameliorated pulmonary damage in a murine model of pneumonia caused by a pathogenic strain of Staphylococcus aureus. These findings suggest that HMGB1 may be an important drug target as scientists, clinical investigators and pharmaceutical companies seek to develop better agents for the treatment of staphylococcal pneumonia. Unfortunately, however, encouraging results from murine models of human disease often fail to translate into positive findings in clinical trials. Thus, before moving from pre-clinical into clinical studies, it may be prudent to validate and extend the recent experimental findings by carrying out additional studies, using a large animal model of pneumonia.