Chorioamnionitis and inflammation of the fetal lung.
OBJECTIVE
Fetal intrauterine exposure to proinflammatory cytokines present in amniotic fluid has been associated with an increased risk of chronic lung disease. However, the impact of histologically confirmed chorioamnionitis on the fetal lung has not yet been elucidated. We therefore investigated cellular immune response, cell proliferation, and messenger ribonucleic acid cytokine expression in fetal pulmonary tissue in the presence or absence of chorioamnionitis.


METHODS
Serial tissue sections were obtained from 27 fetuses at the time of autopsy. Three mothers had received antibiotics for treatment of clinical chorioamnionitis before abortion. Immunohistochemical staining of lung tissue comprised lineage-specific markers (CD68(+), CD3(+), neutrophil elastase). Positively stained cells were evaluated with a graticule, and cells per 5 mm(2) were counted. We undertook in situ hybridization to assess the expression of interleukin 8 messenger ribonucleic acid in the fetal lung.


RESULTS
Seven of 27 fetuses had been exposed to chorioamnionitis. Fetal lungs showed a marked increase in the presence of histologically confirmed chorioamnionitis in densities of CD68(+) macrophages (68 vs 9.5 cells/5 mm(2), median group vs control group; P =.02) and lymphocytes (7 vs 2.5 cells/5 mm(2), median chorioamnionitis vs control group; P =.05) and a similar but lesser increase in neutrophil density (16 vs 4 cells/5 mm(2); difference not significant). Interleukin 8 messenger ribonucleic acid was expressed in 4 of 6 tissue specimens investigated in the chorioamnionitis group. Exposure to chorioamnionitis resulted in interleukin 8 messenger ribonucleic acid expression 7-fold higher than in the nonchorioamnionitis group; however, this difference did not achieve statistical significance.


CONCLUSIONS
Chorioamnionitis was associated with an intrauterine inflammatory response of the fetal lung characterized by a severe infiltration of macrophages, neutrophils, and lymphocytes and also by an increased expression of interleukin 8 messenger ribonucleic acid.
Schmidt
B
B
Department of Neonatology, University of Tübingen, Tubingen, Germany.
Cao
L
L
Mackensen-Haen
S
S
Kendziorra
H
H
Klingel
K
K
Speer
C P
CP
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002821:Chorioamnionitis / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005315:Fetal Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000235:genetics; D019272:Leukocyte Elastase / Q000032:analysis; D008168:Lung / Q000196:embryology / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D016209:Interleukin-8; D019272:Leukocyte Elastase; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule