Instillation of chemotactic factor to silica-injected lungs lowers interstitial particle content and reduces pulmonary fibrosis

Silica-induced pulmonary fibrosis usually follows exposure to increased levels of this particulate and its retention in interstitial macrophages of the lung. It is suggested that accelerated clearance of particles from the pulmonary interstitium may ameliorate subsequent fibrosis. To test this hypothesis, one group of mice received 2-mg intratracheal (IT) silica; some particles were phagocytized and cleared during the subsequent inflammatory response, other particles were translocated across the epithelium to reach interstitial macrophages by 2 weeks. These mice later showed increased fibroblast growth, a doubling of lung collagen levels and large silicotic nodules by 16 weeks when much of the silica was still present in the lung. A second group of mice received IT silica, then 2 and 3 weeks later received IT injections of N-formyl-L-methionyl-leucyl-phenylalanine (FMLP), a leukocyte chemoattractant. Subsequently, a significant increase in inflammatory cells was seen and silica was observed mostly in phagocytes within the alveolar spaces. Few interstitial particles were found at 4 weeks, and extensive fibrosis did not develop by 16 weeks; only a few small nodules were seen and little silica was present in the lung. The results indicate that clearance of interstitial particles by a controlled inflammatory response is possible, and that removal of silica from the interstitium decreases the fibrotic response.