TNF-alpha and IL-1 beta are not essential to the inflammatory response in LPS-induced airway disease

To determine the role of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta in the lower respiratory tract inflammatory response after inha lation of lipopolysaccharide (LPS), we conducted inhalation exposure studie s in mice lacking expression of TNF-alpha and/or IL-1 receptor type 1 and i n mice with functional blockade of these cytokines using adenoviral vector delivery of soluble receptors to one or both cytokines. Alterations in airw ay physiology were assessed by pulmonary function testing before and immedi ately after 4 h of LPS exposure, and the cellular inflammatory response was measured by whole lung lavage and assessment of inflammatory cytokine prot ein and mRNA expression. Airway resistance after LPS exposure was similarly increased in all groups of mice without evidence that blockade of either o r both cytokines was protective from this response. Additionally, all group s of mice demonstrated significant increases in lung lavage fluid cellulari ty with a complete shift in the population of cells to a predominantly neut rophilic infiltrate as well as elevation in inflammatory cytokine protein a nd mRNA levels. There were no significant differences between the groups in measures of lung inflammation. These results indicate that TNF-alpha and I L-1 beta do not appear to have an essential role in mediating the physiolog ical or inflammatory response to inhaled LPS.