Regulatory role of IL-10 in experimental obliterative bronchiolitis in rats.
Obliterative bronchiolitis (OB) affects over half of all chronic human survivors following lung or heart-lung transplantation. Respiratory epithelial cell injury, peribronchial inflammation, and proliferation of fibrovascular connective tissue causing airway occlusion characterize this lesion. Using a rat model of experimental OB, tracheas and mainstem bronchi from Brown-Norway or Lewis (LEW) rats were transplanted subcutaneously into LEW recipients. At 7 days, airway lumens of allografts showed minimal luminal obstruction but significant respiratory epithelial loss. By 14 days, allografts demonstrated marked peribronchial inflammation, nearly complete loss of respiratory epithelium, and extensive intraluminal proliferation of fibrovascular connective tissue, with a mean 58% reduction in airway cross-sectional diameter. However, isografts showed only limited peribronchial inflammation and no loss of airway lumen. When recipients of allotransplants were treated with anti-IL-10, OB developed more rapidly. As early as 7 days, there was marked histologic evidence of OB and a 43% reduction in mean cross-sectional area. Allograft animals that received 5 microg/day of recombinant IL-10 as a constant infusion on day 14 showed almost complete preservation of respiratory epithelium and only mild peribronchial inflammation with only a 15% reduction in airway cross-sectional area. These findings suggest that endogenous IL-10 plays a regulatory role in the development of experimental OB.
Naidu
Babu
B
Department of Cardiothoracic Surgery, University of Washington Medical School, Seattle, Washington 98115, USA.
Krishnadasan
Baiya
B
Whyte
Richard I
RI
Warner
Roscoe L
RL
Ward
Peter A
PA
Mulligan
Michael S
MS
D000818:Animals; D001980:Bronchi / Q000033:anatomy & histology / Q000473:pathology / Q000637:transplantation; D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D014132:Trachea / Q000033:anatomy & histology / Q000473:pathology / Q000637:transplantation; D014184:Transplantation, Homologous
D011994:Recombinant Proteins; D016753:Interleukin-10