DIFFERENTIAL INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN OVINE PULMONARY ALVEOLAR MACROPHAGES FOLLOWING INFECTION WITH CORYNEBACTERIUM-PSEUDOTUBERCULOSIS, PASTEURELLA-HAEMOLYTICA, OR LENTIVIRUSES

Soluble mediators such as tumor necrosis factor alpha (TNF-alpha) may be important in the pathogenesis of many chronic pulmonary infections. We examined the ability of Corynebacterium pseudotuberculosis, Pasteurella haemolytica, and ovine lentiviruses (OvLV) to induce TNF-alpha secretion by pulmonary alveolar macrophages (PAM). Bronchoalveolar lavage cells, composed of greater than 90% PAM, were obtained from normal sheep. Bronchoalveolar lavage cells were cultured for 2, 24, 48, 72, or 168 h in endotoxin-free RPMI medium (with 10% autologous serum) or in medium containing one of the following additives: lipopolysaccharide, 1-mu-m polystyrene beads, C. pseudotuberculosis, P. haemolytica, or one of two plaque-cloned OvLV, 85/28 or 85/34. Lipopolysaccharide, C. pseudotuberculosis, and P. haemolytica induced TNF-alpha-activity in PAM cultures as early as 2 h after inoculation, as assessed by a colorimetric cytotoxicity assay. This activity could be blocked by rabbit anti-recombinant bovine TNF-alpha-serum. In contrast, medium alone, polystyrene beads, and productive infection by OvLV did not induce TNF-alpha-activity in PAM cultures. Bacterial pathogens which infect pulmonary macrophages may elicit the secretion of TNF-alpha within the lungs and lead to the cachectic state associated with chronic pneumonia.