Intratracheal recombinant surfactant protein d prevents endotoxin shock in the newborn preterm lamb.
BACKGROUND
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.


OBJECTIVE
We tested whether treatment with recombinant human SP-D influenced the response of the lung and systemic circulation to intratracheally administered Escherichia coli lipopolysaccharides.


METHODS
After intratracheal lipopolysaccharide instillation, preterm newborn lambs were treated with surfactant and ventilated for 5 h.


METHODS
Survival rate, physiologic lung function, lung and systemic inflammation, and endotoxin level in plasma were evaluated.


RESULTS
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.


CONCLUSIONS
Intratracheal recombinant human SP-D prevented shock caused by endotoxin released from the lung during ventilation in the premature newborn.
Ikegami
Machiko
M
Cincinnati Children's Hospital, Division of Pulmonary Biology, 3333 Burnet Avenue, University of Cincinnati, Ohio 45229-3039, USA. machiko.Ikegami@cchmc.org
Carter
Karen
K
Bishop
Kimberly
K
Yadav
Annuradha
A
Masterjohn
Elizabeth
E
Brondyk
William
W
Scheule
Ronald K
RK
Whitsett
Jeffrey A
JA
D000818:Animals; D000831:Animals, Newborn; D002423:Cause of Death; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D005260:Female; D005865:Gestational Age; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control; D037663:Pulmonary Surfactant-Associated Protein D / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000187:drug effects; D012756:Sheep; D012772:Shock, Septic / Q000517:prevention & control*; D015996:Survival Rate
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants