Abstract |
Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.
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Authors | Suhas G Kallapur, Boris W Kramer, Timothy J M Moss, John P Newnham, Alan H Jobe, Machiko Ikegami, Cindy J Bachurski |
Journal | American journal of physiology. Lung cellular and molecular physiology
(Am J Physiol Lung Cell Mol Physiol)
Vol. 284
Issue 4
Pg. L633-42
(Apr 2003)
ISSN: 1040-0605 [Print] United States |
PMID | 12471018
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endotoxins
- Glucocorticoids
- Interleukin-1
- Interleukin-6
- Interleukin-8
- Serum Amyloid A Protein
- Tumor Necrosis Factor-alpha
- Betamethasone
- Hydrocortisone
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Topics |
- Acute-Phase Reaction
(immunology)
- Animals
- Betamethasone
(pharmacology)
- Bronchoalveolar Lavage Fluid
(cytology, immunology)
- Chorioamnionitis
(drug therapy)
- Drug Synergism
- Endotoxins
- Female
- Gene Expression
(immunology)
- Glucocorticoids
(pharmacology)
- Hydrocortisone
(blood)
- Interleukin-1
(genetics)
- Interleukin-6
(genetics)
- Interleukin-8
(genetics)
- Lung
(embryology, immunology)
- Lymphocyte Count
- Lymphocytes
(cytology)
- Monocytes
(cytology)
- Neutrophils
(cytology)
- Pneumonia
(chemically induced, physiopathology)
- Pregnancy
- Serum Amyloid A Protein
(genetics)
- Sheep
- Tumor Necrosis Factor-alpha
(genetics)
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