Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease.
OBJECTIVE
Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen, the major constituent of lung basement membrane. We studied the effects of chorioamnionitis and antenatal corticosteroids on bronchoalveolar lavage (BAL) fluid levels of MMP-9, and its inhibitor, TIMP-1 in preterm infants.


METHODS
A prospective study was performed on serial BAL samples from 79 ventilated preterm infants at less than 33 weeks' gestation, 18 of whom were from pregnancies complicated by chorioamnionitis. MMP-9 levels were measured by gelatin zymography and TIMP-1 by enzyme-linked immunosorbent assay, and the median value for each infant was calculated. The presence and severity of chorioamnionitis were defined histologically.


RESULTS
BAL fluid MMP-9 levels were higher in preterm infants in the chorioamnionitis group (86 [29-518] vs 13 [3-43] ng/mL, P =.001), and levels increased stepwise with the increasing severity of chorioamnionitis. Antenatal corticosteroids had no effect on median MMP-9 levels. Infants in the chorioamnionitis group were more likely to have chronic lung disease (CLD) develop (55% vs 28%, P <.05). TIMP-1 levels were no different between groups.


CONCLUSIONS
Chorioamnionitis is associated with increased lung type IV collagenase levels in the ventilated preterm infant. Antenatal lung inflammation with up-regulation of MMP-9 may be important in the pathogenesis of CLD.
Curley
Anna E
AE
Department of Child Health, Queen's University of Belfast, Institute of Clinical Science, Belfast, Northern Ireland.
Sweet
David G
DG
Thornton
Claire M
CM
O'Hara
M Denis
MD
Chesshyre
Emily
E
Pizzotti
Jessica
J
Wilbourn
Mark S
MS
Halliday
Henry L
HL
Warner
Jane A
JA
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002821:Chorioamnionitis / Q000150:complications / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007232:Infant, Newborn, Diseases / Q000196:embryology / Q000201:enzymology / Q000209:etiology; D008168:Lung / Q000201:enzymology*; D008171:Lung Diseases / Q000196:embryology / Q000201:enzymology / Q000209:etiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011247:Pregnancy; D011446:Prospective Studies
D020780:Matrix Metalloproteinase 9