title: TNF-alpha and IL-1 beta are not essential to the inflammatory response in LPS-induced airway disease.
abstract: To determine the role of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta 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 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-1 beta do not appear to have an essential role in mediating the physiological or inflammatory response to inhaled LPS.
authors.affiliation: Department of Pediatrics, The University of Iowa, Iowa City, Iowa 52242, USA. jessica-moreland@uiowa.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Moreland
authors.forename: R M
authors.initials: RM
authors.lastname: Fuhrman
authors.forename: C L
authors.initials: CL
authors.lastname: Wohlford-Lenane
authors.forename: T J
authors.initials: TJ
authors.lastname: Quinn
authors.forename: E
authors.initials: E
authors.lastname: Benda
authors.forename: J A
authors.initials: JA
authors.lastname: Pruessner
authors.forename: D A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D007375:Interleukin-1 / Q000235:genetics* / Q000276:immunology*; D007763:Lac Operon; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D053573:Receptors, Interleukin-1 Type I; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D014409:Tumor Necrosis Factor-alpha