Modulation of circulating cell–endothelial cell interaction by erythropoietin in lean and obese mice with cecal ligation and puncture

Abstract

Objective: Septic shock related morbidity is increased further in obese patients. Obese mice have exaggerated inflammatory response compared to lean mice when exposed to cecal ligation and puncture (CLP). The current study employs use of erythropoietin (EPO), an anti-inflammatory agent in obese and lean mice with CLP to study inflammation. Method: Intravital videomicroscopy was used to quantify CLP-induced platelet (PA) and leukocyte (LA) adhesion in cerebral microcirculation of WT (C57Bl/6) and ob/ ob (B6.V- Lepob/J) mice with or without EPO (500 units/kg) treatment. P-selectin expression (P-sel) in various tissues, blood–brain barrier (BBB) and behavioral function and serum tumor necrosis factor (TNF) levels were quantified in these animals. LA, PA, BBB function and P-sel were measured in TNF monoclonal antibody (mAb) pre-treated ob/ ob mice. Results: EPO attenuated the LA, PA, BBB and behavioral dysfunctions and serum TNF levels 4 h after CLP in both WT and ob/ ob mice, and P-sel in ob/ ob CLP mice. Furthermore, TNF mAb and EPO decreased the LA, PA, BBB dysfunction and P-sel in the ob/ ob CLP animals to the same degree. Conclusion: EPO exerts significant anti-inflammatory actions in obese and lean septic mice. Modulation of P-selectin expression via attenuation of TNF production is a suggested underlying mechanism.