IL-10 inhibits inflammation but does not affect fibrosis in the pulmonary response to bleomycin.
Bleomycin yields pulmonary injury characterized by inflammation that proceeds to fibrosis. The production of IL-10 by pulmonary macrophages is increased in the inflammation that accompanies bleomycin lung injury. In the present study, IL-10 deficient and wildtype mice received 0.075 units of bleomycin intratracheally at day 0 and were sacrificed at day 7 or day 14. At day 7, pulmonary inflammation was increased in IL-10-deficient mice as reflected by increased representation of CD3+ and CD4+ lymphocytes and GR-1+ pulmonary granulocytes in the bronchoalveolar lavage (BAL) fluid. Pulmonary interstitial CD80+ and CD86+ mononuclear cells were increased in situ. At day 14, mononuclear cell inflammation was comparable between groups but pulmonary eosinophils were increased in the wildtype. There was no difference in the degree of pulmonary fibrosis, as judged by histology or lung hydroxyproline content. Lung chemokine expression of MIP-1alpha/beta, MIP-2, and eotaxin was increased at days 7 and 14 with a trend towards increased MCP-1 expression at day 14. The findings suggest an immunomodulatory role for IL-10 in the inflammatory response but not in the pulmonary fibrosis yielded by bleomycin.
Kradin
Richard L
RL
The Immunopathology and Pulmonary and Critical Care Units, Massachusetts General Hospital, Boston, MA 02114, USA. rkradin@partners.org
Sakamoto
Hideo
H
Jain
Felipe
F
Zhao
Long-Hai
LH
Hymowitz
Genna
G
Preffer
Frederic
F
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019742:Chemokines, CC / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000503:physiopathology*
D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D019742:Chemokines, CC; D008562:Membrane Glycoproteins; D001761:Bleomycin; D016753:Interleukin-10