title: Surfactant and varespladib co-administration in stimulated rat alveolar macrophages culture.
abstract: Acute lung injury is a life-threatening condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing. sPLA2 activity, free fatty acids, tumour necrosis factor-α (TNF-α) and protein concentrations were measured in culture supernatants. Treatment with varespladib (p=0.019) and varespladib + surfactant (p=0.013), reduced the enzyme activity by approximately 15% from the basal level measured in the untreated cultures. Surfactant, varespladib and varespladib + surfactant, respectively decreased free fatty acids by -45% (p=0.045), - 62% (p=0.009) and -48% (p=0.015), from the baseline concentration of the untreated cultures. Varespladib and poractant- α co-administration reduces sPLA2 activity and free fatty acids release in cultured rat alveolar macrophages, although a clear drug synergy was not evident. Since co-administration may be useful to reduce inflammation and surfactant inactivation in acute lung injury, further in vivo studies are warranted to verify its clinical usefulness.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Luca
authors.forename: Francesca
authors.initials: F
authors.lastname: Vendittelli
authors.forename: Joaquim
authors.initials: J
authors.lastname: Trias
authors.forename: Heather
authors.initials: H
authors.lastname: Fraser
authors.forename: Angelo
authors.initials: A
authors.lastname: Minucci
authors.forename: Leonarda
authors.initials: L
authors.lastname: Gentile
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Gil
authors.forename: Giorgio
authors.initials: G
authors.lastname: Conti
authors.forename: Massimo
authors.initials: M
authors.lastname: Antonelli
authors.affiliation: Lab di Biologia Molecolare Clinica - Serv. Analisi 1, Policlinico Universitario "A.Gemelli", Universita Cattolica del Sacro Cuore, L.go Agostino Gemelli 8, 00168 Roma. daniele.deluca@rm.unicatt.it.
authors.forename: Ettore D
authors.initials: ED
authors.lastname: Capoluongo
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007651:Keto Acids; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000085:Acetates; D005230:Fatty Acids, Nonesterified; D007211:Indoles; D007651:Keto Acids; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; C117948:varespladib; D054497:Phospholipases A2, Secretory