HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 99/6/2204    most recent 00246.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Shashikant, B. N. Articles by Wolfson, M. R. Search for Related Content PubMed PubMed Citation Articles by Shashikant, B. N. Articles by Wolfson, M. R.

Dose response to rhCC10-augmented surfactant therapy in a lamb model of infant respiratory distress syndrome: physiological, inflammatory, and kinetic profiles

¹Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania; ²Nemours Research Lung Center, Alfred I. duPont Hospital for Children, Wilmington, Delaware; and ³Claragen, Inc., College Park, Maryland

Submitted 2 March 2005 ; accepted in final form 28 July 2005

While surfactant (SF) therapy alone improves respiratory distress syndrome (RDS)-associated gas exchange and lung stability, absence of anti-inflammatory proteins limits efficacy with respect to inflammation. Clara cell secretory protein (CC10), deficient in preterm infants, prevents SF degradation and has anti-inflammatory properties. In this study, intratracheal recombinant human (rh) CC10 (Claragen)-augmented SF (Survanta, Ross) therapy was examined in a premature lamb model of RDS with respect to inflammation and kinetic dose-response profiles. Preterm lambs (n = 24; gestational age: 126 ± 3 days) were delivered via cesarean section, sedated, ventilated, and randomized into groups: 100 mg/kg SF, 100 mg/kg SF followed by 0.5 mg/kg rhCC10, 100 mg/kg SF followed by 1.5 mg/kg rhCC10, and 100 mg/kg SF followed by 5.0 mg/kg rhCC10. Arterial blood chemistry and lung mechanics were monitored; lungs were lavaged and snap-frozen after 4 h. TNF-, IL-8 in plasma; TNF-, IL-6, IL-8, myeloperoxidase in lung; and rhCC10 in plasma, urine, bronchoalveolar lavage, and lung were analyzed. Improvement in compliance, peak inspiratory pressure, and ventilatory efficiency index were greatest (P < 0.05) with SF + 5.0 mg/kg rhCC10. Plasma, urine, bronchoalveolar lavage, and lung [rhCC10] (where brackets denote concentration) increased (P < 0.01) with dose. Plasma [IL-8] was lower (P < 0.05) with rhCC10 than SF alone. Treatment with at least 1.5 mg/kg rhCC10 resulted in lower (P < 0.05) lung [TNF-], [IL-8], and [myeloperoxidase]; SF + 1.5 mg/kg rhCC10 group had lower (P < 0.05) lung [IL-6], compared with all other groups. Compared with SF alone, SF augmented with at least 1.5 mg/kg rhCC10 decreased RDS-induced lung and systemic inflammation. Given that inflammation may lead to functional compromise, these data suggest that early intervention with rhCC10 may enhance SF therapy and warrant longer duration studies to determine its role to decrease long-term complications of ventilator management.

Clara cell secretory protein; mechanical ventilation; cytokines; bronchopulmonary dysplasia

This article has been cited by other articles:

				P. Katavolos, C. A. Ackerley, L. Viel, M. E. Clark, X. Wen, and D. Bienzle Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction Vet. Pathol., July 1, 2009; 46(4): 604 - 613. [Abstract] [Full Text] [PDF]

				J. Chen, S. Lam, A. Pilon, A. McWilliams, C. MacAulay, and E. Szabo Higher Levels of the Anti-inflammatory Protein CC10 Are Associated with Improvement in Bronchial Dysplasia and Sputum Cytometric Assessment in Individuals at High Risk for Lung Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1590 - 1597. [Abstract] [Full Text] [PDF]

				A. B. Mukherjee, Z. Zhang, and B. S. Chilton Uteroglobin: A Steroid-Inducible Immunomodulatory Protein That Founded the Secretoglobin Superfamily Endocr. Rev., December 1, 2007; 28(7): 707 - 725. [Abstract] [Full Text] [PDF]