New research shows that the novel cytokine interleukin (IL)-33 reduces sepsis and has “therapeutic potential” to treat this often fatal inflammatory condition. According to the study published this week in Nature Medicine, IL-33 promotes neutrophil recruitment to the site of infection, which is a critical host defence response, and the levels of the decoy IL-33 receptor soluble ST2 in serum could affect whether people recover from sepsis.
Sepsis is a serious illness in which the body has a massive inflammatory response to an infection. Severe sepsis and septic shock can affect multiple organs in the body including the heart, lungs, liver and brain, and is life-threatening (30–50% of people with severe sepsis or septic shock die) and requires treatment in intensive care.
Jose Alves-Filho and colleagues used experimental models of sepsis (using cecal ligation and puncture or CLP) to investigate the role of IL-33 during sepsis. The scientists induced sepsis in mice and then treated them with recombinant IL-33; IL-33-treated mice had a marked reduction in mortality compared to untreated controls and IL-33 protected mice from sepsis for 3h after CLP. The researchers found that IL-33 treatment increased the number of neutrophils migrating to the site of infection (by increasing the expression of the chemokine receptor that is crucial for neutrophil recruitment, CXCR2). This neutrophil recruitment promoted clearance of the bacterial infection and IL-33 also reduced the systemic proinflammatory cytokines (e.g. IL-6, tumour necrosis factor α and CXCL2) that occurred in response to the infective bacteria. Furthermore, the scientists analysed blood serum from healthy individuals and people who had sepsis. They found that people with sepsis had higher levels of IL-33 than healthy people, and that serum levels of soluble ST2 (the decoy receptor of IL-33) were substantially higher in people who did not survive sepsis compared to those who recovered from the disease (soluble ST2 serum levels were negligible in healthy individuals).
The research reveals a “previously unknown mechanism of action of IL-33” and further studies will show whether IL-33 could be used as a potentially novel therapy for sepsis.
Alves-Filho, J., Sônego, F., Souto, F., Freitas, A., Verri, W., Auxiliadora-Martins, M., Basile-Filho, A., McKenzie, A., Xu, D., Cunha, F., & Liew, F. (2010). Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection Nature Medicine DOI: 10.1038/nm.2156