O22 – Oncostatin M modulates immune cell recruitment and bacterial translocation in a murine model of sepsis
Author(s):
Background: Sepsis is a major contributor to inpatient mortality and morbidity worldwide. Understanding the pathogenesis of sepsis is important in the development of new therapeutic modalities. Oncostatin M (OSM) is an immunomodulatory cytokine in the IL-6 family. Prior work in our laboratory demonstrated deficiency of OSM signalling is protective in sepsis, with improvement in survival and end organ injury. The mechanism of OSM in sepsis remains unclear.
Hypothesis: We hypothesize that OSM signalling occurs early on in the onset of sepsis, and is involved in peritoneal immune cell recruitment.
Methods: Littermate OSMR+/+ and OSMR-/- B6.129S-Osmr mice were studied in a fluid-resuscitated variant of the cecal ligation and puncture (CLP) model of sepsis. Using a standardized protocol of 50% cecal ligation and 18 gauge puncture, the mice were observed for a period of 12, 24, and 48 hours, with regular saline administration. Additional groups with shorter time points (0.5 and 1 hour), and standard time points (12-48 hours) without fluid resuscitation were carried out. Following the end point of the fluid-resuscitated groups, peritoneal lavage was performed. Tissue and blood samples were obtained. Cultures of spleen homogenate and whole blood were performed.
Results: All animals (n=42) survived to the standard end points with fluid resuscitation. Without fluid resuscitation, identical animal groups had 50% and 33% mortality at 48 hours, for OSMR+/+ and OSMR-/- respectively (n=6 each). Fluid resuscitation was demonstrated to be adequate, with no significant difference in serum blood urea nitrogen and renal Ngal between all fluid-resuscitated groups. Assessment of bacterial translocation in blood showed higher mean bacterial counts in OSMR-/- animals at 24 and 48 hours (65-fold and 25-fold higher colony counts, respectively). No trends were seen with cultures of spleen homogenate. Peritoneal lavage yielded no significant differences in overall cells counts. Serum levels of OSM increased rapidly after the onset of CLP, with >2-fold increase compared to sham at 0.5 hours (p < 0.05).
Conclusions: Signalling through the OSM/OSMR axis begins early in the onset of CLP. OSM deficiency results in increased bacterial translocation in the setting of intra-abdominal sepsis, which is independent of the survival effects. Understanding this signalling cascade can provide novel strategies for treating intra-abdominal sepsis.