PHYSIOLOGICAL RESEARCH • ISSN 0862-8408 (print) • ISSN 1802-9973 (online)  2017 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic Fax +420 241 062 164, e-mail: physres@fgu.cas.cz, www.biomed.cas.cz/physiolres Physiol. Res. 66 (Suppl. 2): S227-S236, 2017 Selective Inhibition of NF-κB and Surfactant Therapy in Experimental Meconium-Induced Lung Injury J. KOPINCOVA 1,2 , P. MIKOLKA 1,2 , M. KOLOMAZNIK 1,2 , P. KOSUTOVA 1,2 , A. CALKOVSKA 1,2 , D. MOKRA 1,2 1 Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia, 2 Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia Received January 10, 2017 Accepted February 26, 2017 Summary Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there is the need to intervene in both these fields simultaneously, we evaluated therapeutic effect of combination of exogenous surfactant and selective inhibitor of NF-κB (IKK-NBD peptide). Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone or surfactant in combination with IKK-NBD, and oxygen-ventilated for 5 h. PaO 2/FiO2, oxygenation index, oxygen saturation and ventilation efficiency index were evaluated every hour; post mortem, total and differential leukocyte counts were investigated in bronchoalveolar lavage fluid (BALF) and inflammatory, oxidative and apoptotic markers were assessed in lung tissue homogenates. Exogenous surfactant combined with IKK-NBD improved oxygenation, reduced neutrophil count in BALF and levels of IL-1β, IL-6, p38 MAPK and caspase 3 in comparison with surfactant-only therapy. It seems that inhibition of inflammation may be strong supporting factor in surfactant treatment of MAS. Key words Meconium-induced lung injury • Surfactant treatment • NF-κB • Inflammation • IKK-NBD Corresponding author D. Mokra, Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, 036 01 Martin, Slovakia. E-mail: daniela.mokra@jfmed.uniba.sk Introduction Meconium-induced lung injury in newborns is widely associated with pulmonary inflammation. Meconium-stained amniotic fluid contains cytokines capable of triggering immune response (de Beaufort et al. 2003). Complement and toll-like receptors (TLR) 4 activation with subsequent cytokine production had been found in vitro in the presence of meconium (Salvesen et al. 2009, Salvesen et al. 2010). In vivo, polymorphonuclear activation, free radicals production, cytokine synthesis, phospholipase A 2 -mediated tissue damage, cell apoptosis and edema formation accompanied main feature of this disease – surfactant dysfunction (Vydiasagar and Zagaryia 2008, Mikolka et al. 2013, Kopincová et al. 2014). What is clinically manifested as serious respiratory failure with the need of exogenous surfactant and ventilatory support, is on the molecular level largely result of many interrelated signaling pathways streaming through activation of nuclear factor κB (NF-κB; reviewed in Kopincova and Calkovska 2016). Since all these inflammatory processes are able to impair administered exogenous surfactant and mitigate the treatment efficacy, inhibition of inflammation is one of the targets of current therapeutic interventions. https://doi.org/10.33549/physiolres.933678