TY - JOUR
T1 - Pulmonary and systemic inflammatory responses to intraamniotic IL-1alpha in fetal sheep
AU - Kallapur, Suhas
AU - Kramer, Boris
AU - Nitsos, Ilias
AU - Pillow, Jane
AU - Collins, Jennifer
AU - Polglase, Graeme
AU - Newnham, John
AU - Jobe, Alan
PY - 2011
Y1 - 2011
N2 - Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1alpha would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1alpha (100 mug) and were delivered 1, 3, or 7 days later, at 124 +/- 1 days gestation (n=5-8/group). A separate group of sheep were given two intra-amniotic IL-1alpha injections (100 mug dose each): 7 days and again 1 day prior to delivery. IL-1alpha induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H(2)O(2) secretion was increased in inflammatory cells isolated from lungs of IL-1alpha-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1beta, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1alpha exposure. Lung volumes increased 7 days after intra-amniotic IL-1alpha exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1alpha exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1alpha exposure. Compared with a single exposure, exposure to intra-amniotic IL-1alpha 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1alpha is a potent mediator of the fetal inflammatory response syndrome.
AB - Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1alpha would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1alpha (100 mug) and were delivered 1, 3, or 7 days later, at 124 +/- 1 days gestation (n=5-8/group). A separate group of sheep were given two intra-amniotic IL-1alpha injections (100 mug dose each): 7 days and again 1 day prior to delivery. IL-1alpha induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H(2)O(2) secretion was increased in inflammatory cells isolated from lungs of IL-1alpha-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1beta, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1alpha exposure. Lung volumes increased 7 days after intra-amniotic IL-1alpha exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1alpha exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1alpha exposure. Compared with a single exposure, exposure to intra-amniotic IL-1alpha 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1alpha is a potent mediator of the fetal inflammatory response syndrome.
UR - http://ajplung.physiology.org/content/301/3/L285.full.pdf+html
U2 - 10.1152/ajplung.00446.2010
DO - 10.1152/ajplung.00446.2010
M3 - Article
SN - 1040-0605
VL - 301
SP - L285 - L295
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 3
ER -