USE OF ANTI-TNF-ALPHA ANTISERUM TO INVESTIGATE TOXIC ALVEOLITIS ARISING FROM COTTON DUST EXPOSURE

Cotton dust has been associated with byssinosis and toxic alveolitis. A murine animal model has been developed with which to investigate the pathogenesis of these disorders. Studies with the model have reproduc ed the neutrophilic inflammation characteristic of the alveolitis, and have shown the presence of tumor necrosis factor-alpha (TNF-alpha) in the bronchoalveolar lavage (BAL) fluid. The current study investigate d the role of TNF-alpha in the inflammatory response by use of a polyc lonal antiserum to recombinant murine TNF-alpha. Following a 4-h expos ure to cotton dust, experimental animals showed a 40-fold increase in BAL cells with 92% neutrophils. There was a 24-fold increase in TNF-al pha in the BAL fluid. Up regulation of TNF-alpha mRNA expression was d etected in BAL cells. Mice pretreated with anti-TNA-alpha antiserum di splayed a marked attenuation of the neutrophilic inflammation; however , the level of TNF-alpha mRNA expression was not reduced in these mice . These studies support a major role of TNF-alpha in the toxic alveoli tis induced by cotton dust inhalation.