title: Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury.
abstract: Despite the widespread use of exogenous surfactant, acute and chronic lung injury continues to be a major cause of morbidity in preterm infants. CC10 is a protein produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory and antifibrotic properties. We studied whether intratracheal (IT) recombinant human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn piglet model of acute lung injury. Twenty-nine newborn piglets were given Survanta and then ventilated for 48 h receiving the following: room air (group 1); 100% O2 (group 2); or 100% O2 and 25, 5, or 1 mg/kg (groups 3, 4, and 5, respectively) of IT rhCC10 (diluted to 2 mL/kg with saline) at time 0. Laboratory studies, oxygen ratios, static pressure-volume curves, bronchoalveolar lavage (for inflammatory markers), and histologic analyses were performed over the 48-h study period. Pulmonary compliance and oxygenation were significantly improved in animals receiving 5 mg/kg IT rhCC10 compared with room air and 100% O2 controls (p < 0.004 and p < 0.05, respectively, ANOVA). Reductions in inflammatory markers were seen in animals receiving rhCC10, although changes did not reach statistical significance. No significant toxicity was noted. rhCC10 appeared safe and improved pulmonary function in this newborn piglet model of hyperoxic lung injury. We speculate that rhCC10 may represent a promising therapy for the prevention of lung injury in preterm infants.
authors.affiliation: Cardiopulmonary Research Institute, Winthrop-University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA.
authors.forename: Sudhish
authors.initials: S
authors.lastname: Chandra
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Davis
authors.forename: Steven
authors.initials: S
authors.lastname: Drexler
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kowalewska
authors.forename: Darrin
authors.initials: D
authors.lastname: Chester
authors.forename: Hshi-Chi
authors.initials: HC
authors.lastname: Koo
authors.forename: Simcha
authors.initials: S
authors.lastname: Pollack
authors.forename: Richard
authors.initials: R
authors.lastname: Welch
authors.forename: Aprile
authors.initials: A
authors.lastname: Pilon
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Levine
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001688:Biological Products / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008170:Lung Compliance; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012143:Respiratory Physiological Phenomena; D013552:Swine
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C072197:beractant