Elevated Levels of IL-6, INF-γ, And Tnf-α In Mice in Response to Cotton Dust are Modulated by Anti-Tnf-α Antiserum

Abstract

Acute pulmonary neutrophilic inflammation triggered by cotton dust exposure is one of the features of organic dust syndrome. Studies with a mouse model have reproduced the inflammation and have shown the presence of tumor necrosis factor-αlpha (TNF-α) in the bronchoalveolar lavage (BAL) fluid of mice following a 3-h exposure to respirable cotton dust particles. A cover glass technique for cytospin samples of BAL cells resulted in a 42-fold increase in cell count, with 76% neutrophils, 13% lymphocytes, and 10% macrophages, after cotton dust exposure. Immunohistochemical staining of lung specimens with anti-TNF-α antiserum revealed TNF in the cells surrounding pulmonary airways and vessels. Cotton dust exposure resulted in elevated TNF-α, IL-6, and INF-γ in BAL fluid, and INF-γ and IL-6 in serum. Administration of anti-TNF-α antiserum prior to the organic dust exposure resulted in a marked attenuation of the pulmonary inflammatory cell response, as well as decreased IL-6 and TNF-α levels in BAL fluid and decreased IL-6 and INF-γ in serum. These results indicate TNF modulation of the dust-induced toxic alveolitis and cytokine production.