All that glitters may be HMGB1: an interview with Dr. Ulf AnderssonHelene Rosenberg (Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA) interviewed Dr. Ulf Andersson on the occasion of the publication of his research group of the Karolinska Institute (KI) and Karolinska University Hospital, Stockholm, Sweden in the Journal of Leukocyte Biology. Andersson sketches the history of the treatment of rheumatoid arthritis (RA) using gold salts – although “the mechanism of action was never fully determined” – and highlights the importance of the intracellular cytokine HMGB1 whose effect on inflammatory diseases is being investigated by his team. Their findings suggest that gold therapy inhibits nuclear translocation of HMGB1 and the mechanism may have implications for inflammatory diseases beyond RA alone. “We know that HMGB1 is abundantly and aberrantly expressed in synovial tissue in clinical and experimental arthritis and that there has been success in therapeutically targeting HMGB1 in collagen-induced arthritis.” The team already “demonstrated that corticosteroid treatment […] inhibits extracellular HMGB1 release in rheumatoid arthritis and chronic myositis”. The studies of David Pisetsky at Duke University “indicate that the cytokines that most effectively stimulate HMGB1 release also are the most effective at inducing apoptosis of macrophages”. Andersson thinks that “it is certainly possible that the efficacy of gold salts reflects the inhibition of more than one inflammatory pathway”. Their “results suggest that inhibition of HMGB1 release results from the heavy metal component itself”. They also found “that gold salts have an impact on the release of some mediators such as IFNs, but interestingly, not TNF, which is the main target of the biologicals currently in use for the treatment of RA. One can speculate about the profound clinical effects of a combination of a TNF blocker and gold salts since the inhibition of cytokine release would be very broad indeed.” There are likely “many other inflammatory and infectious diseases where HMGB1 release occurs and plays a role in pathogenesis”. So gold salts may play a role here, too, especially if only a short-term administration is needed.
|