TNF-alpha and IL-1beta are not essential to the inflammatory response in LPS-
induced airway disease.
Moreland, Jessica G., Robert M. Fuhrman, Christine L. Wohlford-Lenane, Timothy J.
Quinn, Erin Benda, Jonathan A. Pruessner, and David A. Schwartz.
1Department of Pediatrics and 2Pulmonary, Critical Care, and Occupational Medicine
Division, Department of Internal Medicine, The University of Iowa, Iowa City, Iowa
52242
APStracts 7:0242L, 2000.
To determine the role of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in
the lower respiratory tract inflammatory response after inhalation of lipopolysaccharide
(LPS), we conducted inhalation exposure studies in mice lacking expression of TNF-
alpha and/or IL-1 receptor type 1 and in mice with functional blockade of these cytokines
using adenoviral vector delivery of soluble receptors to one or both cytokines. Alterations
in airway physiology were assessed by pulmonary function testing before and
immediately after 4 h of LPS exposure, and the cellular inflammatory response was
measured by whole lung lavage and assessment of inflammatory cytokine protein and
mRNA expression. Airway resistance after LPS exposure was similarly increased in all
groups of mice without evidence that blockade of either or both cytokines was protective
from this response. Additionally, all groups of mice demonstrated significant increases in
lung lavage fluid cellularity with a complete shift in the population of cells to a
predominantly neutrophilic infiltrate as well as with elevation in inflammatory cytokine
protein and mRNA levels. There were no significant differences between the groups in
measures of lung inflammation. These results indicate that TNF-alpha and IL-1beta do
not appear to have an essential role in mediating the physiological or inflammatory
response to inhaled LPS.
Received 1 February 2000; accepted in final form 9 August 2000
APS Manuscript Number L37-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000