Deficiency in Oncostatin M Receptor Results in Improved Survival in Older Mice following Sepsis through Down-regulation of IL-10
Nour AlMalki, University of Alberta; Saad Salim, University of Alberta; Thomas Churchill, University of Alberta; Rachel Khadaroo, University of Alberta
Sepsis and septic shock are leading causes of multiple organ failure. The role of the anti-inflammatory response in sepsis is not clearly understood. Oncostatin M (OSM) is a novel cytokine part of the IL-6 cytokine family. It has been shown to increase during sepsis and recently linked to influencing interlukin 10 (IL-10) levels in other disease processes. IL-10, a powerful endogenous anti-inflammatory cytokine, decreases the severity of the inflammation by blocking recruitment of inflammatory cells to the site of injury. Hypothesis:
To further understand OSM and IL-10’s role in sepsis, we used OSM receptor (OSMR) knockout mice. We hypothesis that OSMR deficiency regulates the inflammatory, and more specifically, the anti-inflammatory process during sepsis in older mice.Methods:
Sepsis was induced in 50-70 weeks mice via intra-peritoneal injection of cecal slurry (CS) at LD30 of 1.3mg/mg. Mice were observed every 2 hours for 18 hours. Euthanasia and necropsy were performed. Cytokine levels in organ homogenates were measured using Meso Scale Discovery (MSD) multiplex.Results:
Seventy percent of the OSMR knockouts mice had died after 24 hours of CS injection, while none of the WT mice did. Cytokine levels from tissue homogenates in the two groups showed IL-10 expression had remarkably decreased in OSMR-/- mice. Serum, lung and kidney homogenates of the CS treated OSMR -/- group had significantly lower levels of IL-10 than WT. Although levels were not significant in peritoneal lavage and liver homogenates, they had the same trend of being lower in OSMR -/- than WT. Conclusions:
OSMR deficiency results in attenuated lung and kidney IL-10 levels. OSMR deficiency down-regulates the anti-inflammatory response is important in promoting survival in elderly mice following sepsis. Further understanding of the anti-inflammatory response in sepsis will be beneficial in developing novel approaches to therapy.