The role of cyclosporine A and interleukin-2 in obliterative airway disease in a rat tracheal transplant model.
The pathogenesis of obliterative bronchiolitis (OB) following lung and heart-lung transplantation remains unclear. We evaluated the role of CsA and IL-2 on the development of obliterative airway disease (OAD) by administrating exogenous IL-2 in a CsA-treated rat tracheal transplant model. Tracheal grafts were implanted into the peritoneal cavity from Brown Norway (BN) to BN rats or to Lewis (LEW) rats. Allotransplant: No treatment was given in group 1. Short-term CsA (25 mg/kg, i.m. on POD 2 and 3) was used in group 2. Group 3 was treated with long-term CsA (25 mg/kg, i.m. on POD 2 and 3, followed by 5 mg/kg on POD 4 to 27). Administration of IL-2 (300, 000 IU/kg, i.p. on POD 15 to 19 and 22 to 26) was performed to long-term CsA treated rats in group 4. Isotransplant: No treatment was given to group 5, group 6 was treated with IL-2 (same regimen as in group 4). Grafts were harvested at different time points after Tx for histological assessment. No luminal obliteration was observed in group 5 and 6. Complete luminal obliteration was noted 4 weeks after Tx in group 1. In group 2 and 3, obliterative lesion occurred 4-6 weeks after CsA withdrawal. IL-2 increased epithelial loss, lymphocytic infiltration, and obliterative changes in group 4. Our results suggest that OAD is an immune mediated disorder. Furthermore, administration of exogenous IL-2 might be able to abrogate the protection from OAD by CsA therapy.
Gu
Y
Y
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Takao
M
M
Kai
M
M
Lu
L
L
Shimamoto
A
A
Onoda
K
K
Shimono
T
T
Tanaka
K
K
Shimpo
H
H
Shiraishi
T
T
Yada
I
I
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000276:immunology* / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000502:physiology*; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016572:Cyclosporine