Lidocaine increases the anti-inflammatory cytokine IL-10 following mechanical ventilation in healthy mice

BackgroundMechanical ventilation (MV) induces an inflammatory response that may result in (acute) lung injury. Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx. We hypothesized an attenuation of MV-induced inflammatory response with intravenously administered lidocaine. MethodsLidocaine (Lido) (2, 4, and 8mg/kg/h) was intravenously administered during 4h of MV with a tidal volume of 8ml/kg, positive end expiratory pressure 1,5 cmH(2)O and FiO(2) 0.4. We used one ventilated control (CON) group receiving vehicle. After MV, mice were euthanized, and lungs and blood were immediately harvested, and cytokine levels and ICAM-1 levels were measured in plasma and lung homogenates. Pulmonary neutrophils influx was determined in LEDER-stained slices of lungs. Anesthetic need was determined by painful hind paw stimulation. ResultsLidocaine-treated animals (Lido 2, 4 and 8mg/kg/h) showed higher interleukin (IL)-10 plasma levels compared to control animals. Lidocaine treatment with 8mg/kg/h (Lido 8) resulted in higher IL-10 in lung homogenates. No differences were observed in pro-inflammatory cytokines, ICAM-1, and pulmonary influx between the different ventilated groups. ConclusionsIntravenously administered lidocaine increases levels of plasma IL-10 with infusion from 2, 4, and 8mg/kg/h and pulmonary levels of IL-10 with 8mg/kg/h in a murine mechanical ventilation model. Intravenously administered lidocaine appears to reduce anesthetic need in mice.