Tumor necrosis factor and interleukin–1 activities in free lung cells after single and repeated inhalation of bacterial endotoxin. Infect Immun

Bacterial endotoxins (lipopolysaccharides), important components ofmany organic dusts, are known to induce macrophages to produce the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-a). To investigate the role of these mediators in the early inflammatory responses in the lung, guinea pigs were exposed to an aerosol of bacterial endotoxin. A bronchoalveolar lavage (BAL) was then performed, and TNF-a and IL-1 in lysed BAL cells and in the supernatants from BAL cell cultures were studied. The effect of single and repeated LPS inhalation exposures on the activities of TNF and IL-1 was studied, as was the effect of LPS added to the cell culture medium. A single inhalation exposure to LPS caused an increase in the TNF-a and IL-1 activities in cell lysate and in the cell culture supernatant. After a second inhalation exposure, cell-associated and extraceliular TNF-oa activity could not be detected, whereas IL-1 activity was markedly enhanced. IL-1 activity was increased when LPS was added to the cell culture medium with or without a prior inhalation exposure. In contrast, TNF-a activity was not affected after a second exposure. A variety of environmental agents can cause inflammation in the lungs when inhaled. The inflammatory response comprises a series of cellular reactions involving the secre-tion of mediators and invasion and activation of inflamma