Cellular and Cytokine Profiles in Spontaneous Regression Phase of Hypersensitivity Pneumonitis

Abstract

The phase of spontaneous regression of hypersensitivity pneumonitis was evaluated using a mouse model. C57BL/6 mice were instilled intranasally with 150 μg of the thermophilic actionomycete Faeni rectivirgula 3 days a week so as to establish a mouse model of farmer's lungs. It was shown that instillation of mice for a period of more than 6 weeks was associated with a significant decrease in the lung inflammation, suggestive of the so-called spontaneous regression phase seen in this pathology. Indeed, the lung index was seen to decrease after more than 6 weeks of treatment (2.2 after 6 weeks vs. 1.7 at 12 weeks, p < .01). There was also a significant decrease in lung hydroxyproline levels in animals given 12 weeks of treatment (175 μg/lung) compared to 6-week-treated animals (212 μg/lung, p < .05). Treated mice did not show a significant decrease in the alveolitis after 9 weeks of treatment. Also, there was no evidence that there was a decrease in bronchoalveolar lavage macrophage or T lymphocyte activity in mice given more than 9 weeks of F.rectivirgula treatment, as judged by O₂ release and antigen-driven proliferation. Conversely, it was shown that NK cell activity in the lung digest of mice given 9 to 12 weeks of instillation was significantly higher than that seen in mice given 6 weeks of treatment. Analysis of the lung cell cytokine profile seen after ConA mitogenesis showed that after 6 weeks of F.rectivirgula treatments, nonparenchymal cells secreted high levels of tumor necrosis factor alpha (TNFα) and granulocyte macrophage colony-stimulating-factor (GM-CSF), whereas similar cells from the lungs of mice given 9–12 weeks of treatment secreted larger amounts of interferon-gamma (IFNγ) and interleukin-2 (IL-2). Overall, these results suggest that the spontaneous regression phase is associated with changes in NK cell activity and lung cell lymphokine profile.