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United States Department of Agriculture

Agricultural Research Service

Title: Endotoxin Infusion in Anesthetized Sheep Is Associated with Intrapulmonary Sequestration of Leukocytes That Immunohistochemically Express Tumor Necrosis Factor-Alpha

Authors
item Cirelli Rosemary, - THOMAS JEFFERSON UNIV
item Carey Lisa A, - THOMAS JEFFERSON UNIV
item Fisher Jill K, - THOMAS JEFFERSON UNIV
item Rosolia David L, - THOMAS JEFFERSON UNIV
item Elsasser, Theodore
item Caperna, Thomas
item Gee Marlys H, - THOMAS JEFFERSON UNIV
item Albertine Kurt H, - THOMAS JEFFERSON UNIV

Submitted to: Journal of Leukocyte Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 1, 1994
Publication Date: N/A

Interpretive Summary: Bacterial and viral colds and infection are often complicated by the development of injury to lung tissue slowing recovery from disease in animals and man. It is known that during disease stress many white blood cells migrate to the lung to assist in killing invading germs, but in the process of doing so sometimes hormones released from these working cells injure otherwise healthy tissue. One of the hormones responsible for the tissue damage is tumor necrosis factor (TNF), when produced in excess. The role of TNF in the disease process in the lung has not been defined previously. We used a controlled infusion of a bacterial toxin called endotoxin to mimic the actual disease state in sheep and measured the release of TNF into blood and the local accumulation of TNF in lung tissue. The data demonstrate that when cells migrate to the lung to fight disease, they do release TNF locally and this TNF can react with tissues to cause injury. Treatments that can decrease either the amount of TNF released by cells in the lung or the tissue response to TNF should be useful in speeding the recovery from disease stress.

Technical Abstract: Plasma levels of TNF peak between 2h and 4 h during a 12 h continuous infusion of endotoxin in sheep. We hypothesized that a source of this TNF is the pool of activated leukocytes that are sequestered in the lung. Therefore, we physiologically monitored anesthetized sheep during a 4 h baseline and endotoxin infusion. The plasma concentration of TNF peaked at 2 h during the infusion. The plasma concentration of TNF peaked at 2 h during the infusion. Tissue biopsy sections obtained at baseline, and 20 min. 2 and 4 h during endotoxin infusion were stained immunohistochemically with rabbit antibovine TNF polyclonal antibody. Neutrophils and mononuclear cells sequestered in the pulmonary circulation during endotoxin infusion and demonstrated increased cytoplasmic TNF immunoreactivity in situ compared to baseline. We conclude that during endotoxemia, cytokine-producing leukocytes sequester in the lung. These cells likely contribute to the transient rise in circulating levels of TNF in the circulation but also contribute to the development of acute lung injury.

Last Modified: 12/21/2014
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