Murine hypersensitivity pneumonitis: a study of cellular infiltrates and cytokine production and its modulation by cyclosporin A.
The progression of hypersensitivity pneumonitis (HP) was evaluated in mice repeatedly challenged with the actinomycete Faeni rectivirgula (Micropolyspora faeni) (90 or 180 micrograms), at the cellular level and at the mediator level. Instillation of F. rectivirgula by the intranasal route determined a granulomatous inflammation in the lungs of animals correlated with a dramatic increase (5- to 6-fold) in cellularity in the bronchoalveolar space and an increase in the percentage of lymphocytes. Disease in mice was also correlated with high spontaneous release of the cytokines interleukin-1 (IL-1) (60 U/ml), interleukin-6 (IL-6) (72 U/ml), and tumor necrosis factor-alpha (TNF-alpha) (56 U/ml) in the bronchoalveolar lavage (BAL) fluid, as well as by an enhanced capacity for cytokine release by macrophages upon stimulation with F. rectivirgula. It was also found that the pulmonary inflammation was correlated with a 60 to 70% increase in total lung weight after 4 wk and a significant lung fibrosis as seen by a 2-fold increase in lung hydroxyproline levels. Treatment of challenged mice with cyclosporin A (CyA) led to an abrogation of the disease as seen by an abrogation of the increase in lung index, lack of IL-1 and TNF-alpha release in the BAL. CyA did not, however, completely prevent the alveolitis as seen by the cellular infiltrate (2- to 3-fold in BAL cell increase). It also did not prevent the T-lymphocyte recruitment associated with HP, although these cells did not proliferate in response to the F. rectivirgula antigen, in contrast to BAL cells from F. rectivirgula-challenged mice treated with excipient only.(ABSTRACT TRUNCATED AT 250 WORDS)
Denis
M
M
Unité de recherche, Hôpital Laval, Sainte-Foy, Quebec, Canada.
Cormier
Y
Y
Laviolette
M
M
D000281:Administration, Intranasal; D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008848:Micromonosporaceae / Q000276:immunology; D011650:Pulmonary Alveoli / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
D000942:Antigens, Bacterial; D016207:Cytokines; D016572:Cyclosporine