title: Recombinant human Clara cell secretory protein in acute lung injury of the rabbit: effect of route of administration.
abstract: OBJECTIVE
  To test the hypothesis that intratracheal instillation of Clara cell secretory protein (CC 10) to the lung may afford greater protection than intravenous administration from ventilator-induced lung inflammation.
  
  
  METHODS
  Interventional laboratory study.
  
  
  METHODS
  An academic medical research facility in northeastern United States.
  
  
  METHODS
  Sedated, lavage-injured juvenile rabbits.
  
  
  METHODS
  A total of 18 juvenile rabbits were anesthetized, ventilated, injured with saline lavage (Pao2 of <100 mm Hg; respiratory compliance of <0.50 mL.cm H2O.kg and <50% baseline), and randomized to receive intratracheally administered surfactant plus no recombinant human CC 10 (rhCC 10, control), intravenous rhCC 10, or intratracheal rhCC 10.
  
  
  RESULTS
  Arterial blood chemistry and pulmonary mechanics were monitored; plasma and urine were collected serially. After 4 hrs of ventilation, lungs were lavaged and harvested. Surfactant function was analyzed from bronchoalveolar lavage samples (surfactometry); rhCC 10, interleukin-8, and lung myeloperoxidase concentrations were measured. Pao2, oxygenation index, ventilatory efficiency index, and respiratory compliance were not different across time or group beyond injury. Surfactometry data identified no differences as a function of group or time. Plasma, bronchoalveolar lavage, and lung interleukin-8 concentrations, lung myeloperoxidase concentrations, and inflammatory cell counts in the alveolar and interstitial spaces of intravenous and intratracheal groups were lower than in the control group (p < .05) but not statistically different from each other. Concentrations of rhCC 10 in lung, bronchoalveolar lavage, and plasma were greater in the intratracheal group than in the intravenous group (p<.05). Urine rhCC 10 concentrations were greater for the intravenous group than for the intratracheal group (p<.05) at 1, 3, and 4 hrs after treatment. No group differences in histomorphometry were noted.
  
  
  CONCLUSIONS
  Both intravenous and intratracheal rhCC 10 delivery, after surfactant therapy, effectively decrease lung inflammation vs. surfactant alone. While supporting the physiologic profile, intratracheal instillation results in greater, maintained lung and plasma rhCC 10 pools compared with intravenous administration. As such, intratracheal instillation of rhCC 10 may afford more prolonged protection against lung inflammation than intravenous administration.
authors.affiliation: Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Miller
authors.forename: Beth N
authors.initials: BN
authors.lastname: Shashikant
authors.forename: James M
authors.initials: JM
authors.lastname: Melby
authors.forename: Aprile L
authors.initials: AL
authors.lastname: Pilon
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Shaffer
authors.forename: Marla R
authors.initials: MR
authors.lastname: Wolfson
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D014598:Uteroglobin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D018836:Inflammation Mediators; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin