TNF-␣ and IL-1␤ are not essential to the inflammatory response in LPS-induced airway disease. Am J Physiol Lung Cell Mol Physiol 280: L173-L180, 2001.-To determine the role of tumor necrosis factor (TNF)-␣ and interleukin (IL)-1␤ in the lower respiratory tract inflammatory response after inhalation of lipopolysaccharide (LPS), we conducted inhalation exposure studies in mice lacking expression of TNF-␣ and/or IL-1 receptor type 1 and in mice with functional blockade of these cytokines using

more »

... oviral 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-␣ and IL-1␤ do not appear to have an essential role in mediating the physiological or inflammatory response to inhaled LPS. tumor necrosis factor-␣; interleukin-␤; lipopolysaccharide; endotoxin; cytokines; asthma; airway inflammation ENDOTOXIN OR LIPOPOLYSACCHARIDE (LPS) is present in varying concentrations in the air we breathe and both causes and exacerbates airway disease. Among workers exposed to organic dusts, the concentration of endotoxin in the bioaerosol is associated with the development and progression of airway disease (15, 20, 35) . Exposure to dusts causes a variety of acute respiratory problems including wheezing, dyspnea, and decreased airflow (26). Recent reports (29, 30) have indicated that the concentration of endotoxin in the domestic setting