Background: Sepsis remains a major cause of morbidity and mortality. A variety of strategies targeting modulation of the pro-inflammatory response associated with early sepsis have been reported without clinical success. GLP-1 enhances glucose-stimulated insulin secretion. In addition, it was shown to have anti-inflammatory effects. We hypothesized that treatment with exendin-4, a GLP-1 receptor agonist, would attenuate inflammation and improve glucose control in a lipopolysaccharide (LPS) rat model of inflammation. Methods: Two-month-old male Wistar rats were randomly assigned to one of the following four groups: 1) treatment: intraperitoneal (IP) injection of LPS 10 mg/kg followed by exendin-4, 30 µg/kg, 10 minutes later; 2) control-1: IP injection of LPS 10 mg/kg, followed by normal saline (NS); 3) control-2: IP NS injection followed by exendin-4; 4) sham: IP injection of NS followed by another NS injection. Glucose concentration, total white blood count with absolute neutrophil count, and pro- and anti-inflammatory cytokine concentrations were measured at 0, 3, 6, and 10 hours following LPS injection. Results: At 3 hours, rats injected with LPS developed neutropenia, elevated pro- and anti-inflammatory cytokines, and mild hypoglycemia. Treatment with exendin-4 significantly modulated neutropenia, and decreased pro-inflammatory cytokine concentrations (IL-1α, IL-1β, IL-6, TNFα, and IFNγ). However, exendin-4 had no effect on IL-10 concentrations. LPS injection led to mild hypoglycemia, that was not observed in rats treated with exendin-4. Sham animals exhibited no significant change from baseline in all parameters. Conclusion: In this LPS model of acute early phase inflammation, treatment with exendin-4 decreased pro-inflammatory cytokine concentrations without changing IL-10 blood levels and improved neutropenia. Following LPS injection, rats developed a tendency toward hypoglycemia that improved with exendin-4. Overall our data suggest that exogenous exendin-4 mediates anti-inflammatory effects early in this rat model of endotoxin-induced inflammation.

Acute lower respiratory tract infections are a leading cause of death in individuals under the age of 5 years, mostly in low- and middle-income countries (LMICs). The lack of respiratory support systems contributes to the poor outcomes. Bubble CPAP is widely used for non-invasive respiratory support, but sicker children often require support over what CPAP provides in the form of BiPAP. We developed and tested a simple bubble-based bilevel ventilator (Bubble bi-vent) and compared it with a standard care BiPAP device. The bubble bilevel device consisted of a single tube submerged in a water-sealed column to maintain end-expiratory positive airway pressure. It moves vertically via an electric motor to also provide inspiratory positive airway pressure for augmentation of lung volumes, with the duration and frequency of breaths controlled by a microprocessor. We tested this novel device in passively breathing mechanical lung models for infants and small children. We compared pressure and tidal volume delivery between the novel device and a Trilogy BiPAP ventilator. The results showed that the Bubble bi-vent could deliver set pressures in a mechanical lung and was comparable to a standard Trilogy ventilator. While two different bubble-based bilevel pressure devices have been piloted for neonates and adults, our results demonstrate the feasibility of bubble bilevel ventilation for infants and small children with moderate to severe lung disease for whom this was previously not described.