Background: Our population is rapidly aging and the frail elderly patients with multiple coexisting comorbidities, repeated and prolonged hospital stays are most susceptible to sepsis and increased admissions to ICUs. Sepsis with concomitant multiple organ failure continues to be a clinical challenge, especially in our elderly patient above 65 years old. Furthermore, the morbidity and mortality due to sepsis has been increasing especially in this susceptible population. Sixty percent of the elderly patients affected with sepsis die from septic shock. The immune system in the elderly is different from younger individuals, with functional impairments in cell-mediated and innate immunity. As such, studying this immunological difference might provide insight into the inflammatory processes of sepsis, and more importantly, provide novel treatment strategies for our elderly population.
Oncostatin M: Oncostatin M (OSM) is part of the IL-6 cytokine family that has been shown to have pleiotropic functions in hematopoiesis, immunologic and inflammatory networks. There is an increase in the levels of OSM in patients experiencing septic shock. Despite identification and cloning of human OSM, there is still a considerable amount that is not clear about its biology, function in vivo, and its contradictory role under certain conditions. Our group has mice that have homologous knockout of the OSM receptor (OSMR). This knockout strain hinders the OSM cytokine pathway.
Objectives: Our objective was to examine how deficiency in OSM receptor (OSMR) contributes to the inflammatory process in sepsis, especially in elderly. To study this, we are using murine models of sepsis, via peritoneal injection of cecal contents. This model mimics peritonitis. Old mice are compared to younger mice and the inflammatory processes are dissected.
Figure: Clinical Score of Young and Old Mice Following Peritonitis. Mice were given IP injection of cecal slurry and were observed for 18 hours. Clinical score measuring appearance, activity, respiratory rate, eyes and response to stimulus were recorded every 2 hours. The higher the score, the worse off the mice were. We saw that the younger mice had an earlier response to the cecal content injection. Though there was a delayed response in the old wildtype OSMR+/+ mice, it had a worse outcome than the old OSMR-/- mice. This illustrates that OSMR deficiency does provided protection against sepsis and improves on clinical outcomes, especially in older mice.