New therapies for sepsis: focus on the interleukin (IL)12 family member IL27.

Sepsis is a severe complication of abdominal infections such as peritonitis and is associated with high mortality. Unfortunately, the molecular mechanisms controlling the development of sepsis are still incompletely understood. Interestingly, the interleukin (IL) 12 family member IL27 seems to play a key role in sepsis. In a murine model of septic peritonitis induced by caecal ligation and puncture (CLP), IL27 levels were found to be strongly induced. Furthermore, mice deficient for the EBI3 subunit of IL27 were resistant to CLP-induced septic peritonitis as compared to wild-type controls. This effect could be suppressed by injection of recombinant IL27. Further studies demonstrated that IL27 directly suppresses endotoxin-induced production of reactive oxygen intermediates by isolated primary murine granulocytes. The significance of this observation was underlined by studies on in vivo blockade of IL27 function using a newly designed soluble IL27 receptor fusion protein (sWSX-Fc). Such treatment led to significantly increased survival after CLP as compared to control-treated mice. These findings indicate that IL27 is an important negative regulator of innate immune cells in septic peritonitis. Blockade of IL27 function could be an interesting novel approach for the treatment of patients with sepsis.