Elevated levels of IL-6, INF-gamma, and TNF-alpha in mice in response to cotton dust are modulated by anti-TNF-alpha 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-alpha (TNF-alpha) 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-alpha antiserum revealed TNF in the cells surrounding pulmonary airways and vessels. Cotton dust exposure resulted in elevated TNF-alpha, IL-6, and INF-gamma in BAL fluid, INF-gamma and IL-6 in serum. Administration of anti-TNF-alpha 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-alpha levels in BAL fluid and decreased IL-6 and INF-gamma in serum. These results indicate TNF modulation of the dust-induced toxic alveolitis and cytokine production.