A new candidate compound against inflammatory disorders

Eight years ago researchers in Berlin discovered that polymorphonuclear leukocytes, shortly neutrophils can, in additon to internalization, kill microbes extracellularly by releasing so called Neutrophil Extracellular Traps (NETs). These web-like structures consist of nuclear chromatin that is decorated with proteases, antimicrobial peptides and pro-inflammatory proteins. Early on it has been suggested that these NETs serve a beneficial role during acute infections. However, there is an increasing body of evidence that NETs additionally have hazardous effects in inflammation-related disorders, such as Small Vessel Vasculitis, Systemic Lupus Erythematosus or Transfusion-related Acute Lung Injury. It is therefore crucial to find new phamacological inhibitors of NET formation that might be future therapeutics for these diseases.

The UCMR research group of Constantin Urban has now found out that the membrane-permeable radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) efficiently inhibits NET release. This compound has very low toxicity and is already in clinical trials as prophylaxis against radiation damage. Tempol is therefore a very promising candidate as anti-NET therapy. The work has been recently published in the Journal Frontiers in Immunology (link: http://www.frontiersin.org/Molecular_Innate_Immunity/10.3389/fimmu.2012.00391/abstract ).