Anti-IL-8 antibody potentiates the effect of exogenous surfactant in respiratory failure caused by meconium aspiration

ABSTRACT

Aim: Meconium aspiration syndrome (MAS) is life-threatening respiratory failure of newborns which can be treated by exogenous surfactant. In response to meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil infiltration of the lungs. Local accumulation and activation of neutrophils, on-going inflammation, lung edema, and oxidative damage contribute to inactivation of endogenous and therapeutically given surfactants. Therefore, we have hypothesized that addition of monoclonal anti-IL-8 antibody into exogenous surfactant can mitigate the neutrophil-induced local injury and the secondary surfactant inactivation and may finally result in improvement of respiratory functions. Methods: New Zealand rabbits with intratracheal meconium-induced respiratory failure (meconium 25 mg/ml, 4 ml/kg) were divided into three groups: untreated (M), surfactant-treated (M + S), and treated with combination of surfactant and anti-IL-8 antibody (M + S + anti-IL-8). Surfactant therapy consisted of two lung lavages with diluted porcine surfactant Curosurf (10 ml/kg, 5 mg phospholipids (PL)/ml) followed by undiluted Curosurf (100 mg PL/kg) delivered by means of asymmetric high-frequency jet ventilation (f. 300/min, Ti 20%). In M + S + anti-IL-8 group, anti-IL-8 antibody (100 µg/kg) was added directly to Curosurf dose. Animals were oxygen-ventilated for additional 5 h, respiratory parameters were measured regularly. Subsequently, cell counts in bronchoalveolar lavage fluid (BAL), lung edema formation, oxidative damage, levels of interleukins (IL)-1β and IL-6 in the lung homogenate were evaluated. Results: Surfactant instillation significantly improved lung function. Addition of anti-IL-8 to surfactant further improved gas exchange and ventilation efficiency and had longer-lasting effect than surfactant-only therapy. Combined treatment showed the trend to reduce neutrophil count in BAL fluid, local oxidative damage, and levels of IL-1β and IL-6 more effectively than surfactant-alone, however, these differences were not significant. Conclusion: Addition of anti-IL-8 antibody to surfactant could potentiate the efficacy of Curosurf on the gas exchange in experimental model of MAS.

KEYWORDS:

• anti-IL-8/anti-CXCL8 antibody
• exogenous surfactant
• lung functions
• meconium aspiration syndrome
• respiratory failure

Acknowledgments

The authors thank M. Petraskova, M. Hutko, D. Kuliskova, and Z. Remisova for technical assistance.

Declaration of interests

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

The study was supported by projects APVV-0435-11, APVV-15-0075, VEGA 1/0305/14, VEGA 1/0356/18, and the project “Biomedical Center Martin” (ITMS code 26220220187), co-financed from EU sources.