Vasopressin decreases sepsis-induced pulmonary inflammation through the V2R

SummaryThe early use of vasopressors in sepsis has been associated with a decrease in immune activation independent of hemodynamic effects, although the mechanism behind this remains unclear. We hypothesize that low dose vasopressin will reduce the pulmonary inflammation associated with sepsis. Our aims were to (1) determine whether vasopressin reduces lipopolysaccharide (LPS)-induced pulmonary inflammation and (2) determine which vasopressin receptor is responsible for pulmonary immune modulation. Mice were treated with intraperitoneal LPS to induce both systemic and pulmonary inflammation. Vasopressin or saline was infused via peritoneal pump and interleukin 6 (IL-6) in lung and serum was measured at 6 h. NF-κB activation as was determined in the lung through immunoblotting total and phospho-IκB. Hemodynamic data was also obtained at the 6 h mark. In a separate series of experiments mice received both LPS and vasopressin infusion following pretreatment with vasopressin receptor antagonists to V1R, V2R and OTR. Low dose LPS dramatically raises both serum IL-6 and pulmonary levels of IL-6 and phospho-IκB despite no significant changes in mean arterial pressure at 6 h. Compared to saline, vasopressin infusion significantly decreases both the pulmonary IL-6 levels and phospho-IκB in LPS treated mice without raising arterial pressure. Pretreatment with V2R antagonist results in complete attenuation of vasopressin's immunosuppressive effects, with restoration of pulmonary IL-6 and phospho-IκB levels to those seen with LPS alone.ConclusionsVasopressin exerts a local anti-inflammatory effect on the lung through the V2R in a model of sepsis.