Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

Abstract

During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1–3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.

Cooperative action of SP-A and its trimeric recombinant fragment with polymyxins against Gram-negative respiratory bacteria

“…Aggregation of LPS by SP-A or PMB blocks LPS interaction with its receptor complex, which reduces proinflammatory cytokine production ( 16 , 57 ). Furthermore, in the lung, LPS promotes destabilization and alteration of the biophysical activity of pulmonary surfactant ( 89 ), and SP-A and PME act as a scavenger of LPS, protecting pulmonary surfactant from the inhibitory effects of LPS ( 90 ).…”

“…Importantly, it has recently been shown, in an animal model of pneumonia, that instillation of colistin mixed with exogenous pulmonary surfactant increases its bactericidal effect compared to instillation of colistin alone, suggesting that lung surfactant may serve as a vehicle to facilitate the efficient spread of colistin through the airways ( 98 ). We suggest that therapeutic SP-A/colistin complexes mixed with exogenous surfactant might be beneficial in treating resistant Gram-negative bacterial infections and protecting pulmonary surfactant from the inhibitory effects of LPS ( 90 ).…”

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure

“…PxB improved the positive effect of EPS on inflammation and oxidative stress in mechanically ventilated rats with LPSinduced acute lung injury. 35 Calkovska et al 36 proved the synergetic effect of surfactant therapy (Curosurf) enriched with PxB in a double hit model of neonatal lung injury of immature rabbits. Independently, the authors evaluated changes in the surface activity of the surfactant exposed to smooth LPS without and with PxB by using a captive bubble surfactometer.…”