Chronic experimental interstitial pneumonitis in the rabbit.

The effects on the lungs of chronic aerosol and intravenous antigen challenges in preimmunized and control rabbits were studied. Soluble and particulate antigens included ovalbumin, keyhole limpet hemocyanin, antigen-adsorbed latex particles, glutaraldehyde cross-linked ovalbumin, and killed bacille Calmette-Guérin (BCG). Despite the development of acute alveolitis in sensitized animals, chronic aerosol challenge with both soluble and particulate antigens failed to produce chronic interstitial lung disease. Chronic intravenous challenge with killed BCG, but not other particulate antigens, resulted in a progressive interstitial pneumonitis, with evidence of fibrogenesis in animals that had been presensitized to tuberculin by toepad injection of complete Freund's adjuvant. Adaptive alveolar clearance mechanisms thus appear to protect rabbits from chronically inhaled antigen. Pulmonary circulatory clearance of BCG, however, results in an interstitial pneumonitis that is dependent on previous sensitization.