IL-12p40(-/-) mice treated with intratracheal bleomycin exhibit decreased pulmonary inflammation and increased fibrosis.
Pulmonary lymphohistiocytic inflammation and fibrosis characterize bleomycin (BLM) lung injury. IL-12, a p70 cytokine produced primarily by macrophages and dendritic cells, promotes T-helper-1-mediated inflammation. IL-12 production by blood monocytes and bronchoalveolar large mononuclear cells (BAMC) was investigated at Days 1-14 following intratracheal administration of BLM. In the lung, BAMC showed a large peak of IL-12 expression at Day 5 that returned rapidly toward baseline. IL-12p40(-/-) mice treated with BLM intratracheally showed less pulmonary mononuclear cell inflammation at Day 7 than wild-type controls, whereas pulmonary fibrosis and hydroxyproline content were increased in IL-12p40(-/-) mice at Day 14. The expression of IP-10, RANTES, and eotaxin were decreased in IL-12p40(-/-) mice and lung IL-6 expression was increased, all compared to controls. We conclude that IL-12 promotes the lymphohistiocytic response to BLM and may inhibit the late development of pulmonary fibrosis.
Sakamoto
Hideo
H
Immunopathology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Zhao
Long-Hai
LH
Jain
Felipe
F
Kradin
Richard
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D013154:Spleen / Q000166:cytology
D000900:Anti-Bacterial Agents; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D015850:Interleukin-6; D001761:Bleomycin; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D006909:Hydroxyproline