Cellular and cytokine profiles in spontaneous regression phase of hypersensitivity pneumonitis.
The phase of spontaneous regression of hypersensitivity pneumonitis was evaluated using a mouse model. C57BL/6 mice were instilled intranasally with 150 micrograms of the thermophilic actinomycete 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 micrograms/lung) compared to 6-week-treated animals (212 micrograms/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 (TNF alpha) 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 (IFN gamma) 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.
Denis
M
M
Unité de Recherche Pulmonaire, Centre Hospitalier de l'Université de Sherbrooke, Québec, Canada.
Bisson
D
D
Ghadirian
E
E
D000542:Alveolitis, Extrinsic Allergic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000942:Antigens, Bacterial; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008848:Micromonosporaceae / Q000276:immunology; D012075:Remission, Spontaneous
D000942:Antigens, Bacterial; D016207:Cytokines