IL-12 modulates expression of hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes. Only a minority of individuals exposed to these Ags develops disease, suggesting that host factors are important for the expression of HP. We compared the expression of HP in a sensitive strain of mice, C57BL/6, and in a resistant strain of mice, DBA/2. They were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) or to saline alone for 3 consecutive days/week for 3 wk. After exposure to Ag, C57BL/6 mice, but not DBA/2 mice, developed granulomatous inflammation with an increase in lung index (lung weight). Both strains had similar amounts of Ag delivered to the lungs after intranasal installation, as determined with 14C-labeled Ag. Both also had similar increases in total bronchoalveolar cells after Ag exposure, but the C57BL/6 mice had more lymphocytes. Compared with the resistant strain, the sensitive strain had a significantly greater Ag-induced increase in IL-12 and IFN-gamma gene expression. DBA/2 mice resembled sensitive, C57BL/6 mice if they received IL-12 augmentation therapy at the time of Ag exposure. These findings were not limited to lung, since both unstimulated and SR-stimulated spleen cells from C57BL/6 mice released significantly more IL-12 than cells from DBA/2 mice. However, spleen cells from DBA/2 mice made more IFN-gamma when exposed to IL-12, than cells from C57BL/6 mice. These results suggest that the IL-12 response to Ag may modulate in part the expression of HP.
Gudmundsson
G
G
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, Iowa City 52242, USA. gunnar-gudmundsson@uiowa.edu
Monick
M M
MM
Hunninghake
G W
GW
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology; D000280:Administration, Inhalation; D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016930:Saccharopolyspora / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma