Intratracheal Recombinant Surfactant Protein D Prevents Endotoxin Shock in the Newborn Preterm Lamb

• Published in: American journal of respiratory and critical care medicine 2006-06, Vol.173 (12), p.1342-1347
• Main Authors: Ikegami, Machiko, Carter, Karen, Bishop, Kimberly, Yadav, Annuradha, Masterjohn, Elizabeth, Brondyk, William, Scheule, Ronald K, Whitsett, Jeffrey A
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Animals, Newborn; B. Critical Care; Biological and medical sciences; Blood and lymphatic vessels; Body temperature; Cardiology. Vascular system; Catheters; Cause of Death; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E coli; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Endotoxins - blood; Escherichia coli; Female; Gestational Age; Humans; Immune system; Infections; Inflammation; Intensive care medicine; Interleukin-1 - analysis; Interleukin-6 - analysis; Interleukin-8 - analysis; Intubation, Intratracheal; Lipopolysaccharides - blood; Lipopolysaccharides - pharmacology; Lung - blood supply; Lung - drug effects; Lungs; Male; Medical sciences; Newborn babies; Pathogens; Pneumonia - etiology; Pneumonia - prevention & control; Premature babies; Proteins; Pulmonary Surfactant-Associated Protein D - therapeutic use; Pulmonary Surfactants - therapeutic use; Respiration, Artificial; Respiratory Mechanics - drug effects; Sepsis; Sheep; Shock, Septic - prevention & control; Surfactants; Survival Rate; Ventilators
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200509-1485OC

The susceptibility of neonates to pulmonary and systemic infection has been associated with the immaturity of both lung structure and the immune system. Surfactant protein (SP) D is a member of the collectin family of innate immune molecules that plays an important role in innate host defense of the lung. We tested whether treatment with recombinant human SP-D influenced the response of the lung and systemic circulation to intratracheally administered Escherichia coli lipopolysaccharides. After intratracheal lipopolysaccharide instillation, preterm newborn lambs were treated with surfactant and ventilated for 5 h. Survival rate, physiologic lung function, lung and systemic inflammation, and endotoxin level in plasma were evaluated. In control lambs, intratracheal lipopolysaccharides caused septic shock and death associated with increased endotoxin in plasma. In contrast, all lambs treated with recombinant human SP-D were physiologically stable and survived. Leakage of lipopolysaccharides from the lungs to the systemic circulation was prevented by intratracheal recombinant human SP-D. Recombinant human SP-D prevented systemic inflammation and decreased the expression of IL-1beta, IL-8, and IL-6 in the spleen and liver. Likewise, recombinant human SP-D decreased IL-1beta and IL-6 in the lung and IL-8 in the plasma. Recombinant human SP-D did not alter pulmonary mechanics following endotoxin exposure. Recombinant human SP-D was readily detected in the lung 5 h after intratracheal instillation. Intratracheal recombinant human SP-D prevented shock caused by endotoxin released from the lung during ventilation in the premature newborn.