Minimal lung and systemic responses to TNF-alpha in preterm sheep.
TNF-alpha has been associated with chorioamnionitis and the subsequent development of bronchopulmonary dysplasia in preterm infants. We asked whether bioactive recombinant ovine TNF-alpha could induce chorioamnionitis, lung inflammation, lung maturation, and systemic effects in fetal sheep. We compared the responses to IL-1alpha, a cytokine known to induce these responses in preterm sheep. Intra-amniotic TNF-alpha caused no chorioamnionitis, no lung maturation, and a very small increase in inflammatory cells in the fetal lung after 5 h, 2 days (d), and 7 d. In contrast, IL-1alpha induced inflammation and lung maturation. TNF-alpha given into the airways at birth increased granulocytes in the bronchoalveolar lavage fluid of ventilated preterm lungs and decreased the mRNA for surfactant protein C but did not adversely effect postnatal lung function. An intravascular injection of IL-1alpha caused a systemic inflammatory response in fetal sheep, whereas there was no fetal response to intravascular TNF-alpha. Fetal and newborn preterm sheep are minimally responsive to TNF-alpha. Therefore, the presence of a mediator such as TNF-alpha in a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals.
Ikegami
Machiko
M
Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. machiko.ikegami@cchmc.org
Moss
Timothy J M
TJ
Kallapur
Suhas G
SG
Mulrooney
Neil
N
Kramer
Boris W
BW
Nitsos
Ilias
I
Bachurski
Cindy J
CJ
Newnham
John P
JP
Jobe
Alan H
AH
D000653:Amniotic Fluid; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002821:Chorioamnionitis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005865:Gestational Age; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D012121:Respiration, Artificial; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha