ELEVATED LEVELS OF IL-6, INF-GAMMA, AND TNF-ALPHA IN MICE IN RESPONSETO COTTON DUST ARE MODULATED BY ANTI-TNF-ALPHA ANTISERUM

Acute pulmonary neutrophilic inflammation triggered by cotton dust exp osure is one of the features of organic dust syndrome. Studies with a mouse model have reproduced the inflammation and have shown the presen ce of tumor necrosis factor-alpha (TNF-alpha) in the bronchoalveolar l avage (BAL) fluid of mice following a 3-h exposure to respirable cotto n dust particles. A cover glass technique for cytospin samples of BAL cells resulted in a 42-fold increase in cell count, with 76% neutrophi ls, 13% lymphocytes, and 10% macrophages, after cotton dust exposure. Immunohistochemical staining of lung specimens with anti-TNF-alpha ant iserum revealed TNF in the cells surrounding pulmonary airways and ves sels. Cotton dust exposure resulted in elevated TNF-alpha, IL-6, and I NF-gamma in BAL fluid, and INF-gamma and IL-6 in serum. Administration of anti-TNF-alpha antiserum prior to the organic dust exposure result ed in a marked attenuation of the pulmonary inflammatory cell response , as well as decreased IL-6 and TNF-alpha levels in BAL fluid and decr eased IL-6 and INF-gamma in serum. These results indicate TNF modulati on of the dust-induced toxic alveolitis and cytokine production.