Long-term evolution of BCG- and CFA-induced granulomas in rat lungs. Correlation of histologic features with cells in...

Granulomatous inflammation was induced in the lungs of rats for assessment of the suitability of this animal species for long-term study of granuloma development and resolution and for comparison of the histologic changes with the cellular profile in bronchoalveolar lavage (BAL) samples. It was found that after a single intravenous injection of bacillus Calmette-Guérin (BCG) organisms suspended in saline-0.01% Triton, complete Freund's adjuvant (CFA), or BCG suspended in CFA (BCG + CFA), distinct pathologic patterns developed in the lungs during the acute stages. BCG alone caused numerous small epithelioid granulomas associated with interstitial infiltration; CFA alone caused large discrete granulomas with minimal interstitial changes, and BCG + CFA caused large granulomas associated with diffuse interstitial infiltration. Following CFA or BCG + CFA the maximum number and size of granulomas were reached approximately 4 weeks after injection. By 8 weeks collagen was seen in the larger granulomas in sections stained with hematoxylin and eosin from animals given CFA or BCG + CFA. Maximum collagen deposition was seen at 16 weeks. From that point onward the degree of collagen deposition decreased, so that by approximately 42 weeks collagen was no longer seen. At 52 weeks residual granulomatous lesions consisted of a few foci of foamy macrophages surrounded by several layers of lymphocytes or epithelioid cells surrounded by dense layers of lymphocytes. Bronchoalveolar lavage samples revealed that at all time periods the number of leukocytes was increased and that the increase was due primarily to an influx of macrophages and lymphocytes. The increase in number of lymphocytes was so striking that at the peak of granulomatous changes following injection of BCG + CFA up to 50% of the total cells were found to be lymphocytes. The total number of leukocytes in BAL samples and the absolute number of lymphocytes closely paralleled the intensity of histologic changes seen in microscopic sections. It is concluded that the intravenous injection of BCG, CFA, or BCG + CFA in rats causes distinct and profound granulomatous patterns that are associated with increased cellularity in BAL samples. The findings suggest that the rat may be an excellent model for study of the mechanisms of granuloma development and resolution.