Development of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment.
BACKGROUND
Chronic allograft failure represents the major cause of late morbidity and mortality after solid organ transplantation. Despite the pathological and clinical changes of this disease being well-described, the etiology and the causative factors are still under discussion. Several clinical, as well experimental studies, emphasize the significance of acute rejection. In rat model of left lung allo-transplantation (F344-to-WKY) the influence of acute rejection (AR) on the development of chronic rejection (CR) was studied.


METHODS
In Group I (n = 25) no immunosuppression was used, while methylprednisolone (MP) (10 mg/kg) was applied in Group II (n = 20) in the early phase of AR on postoperative Days 9, 10, 11 and in Group III (n = 20) during AR on Day 14, Day 15, Day 16. The rats were sacrificed on Day 5, Day 15/20, Day 30, Day 60, Day 100 and following HE-staining the extend of AR as well CR was graded according to the working formulation of The International Society of Heart and Lung Transplantation.


RESULTS
In Group I, AR was found at Day 15 and Day 30 which resolved spontaneously and resulted in CR on Day 60 and Day 100. In Group II, signs of AR were less evident on Day 20, while mild AR persisted on Day 30 and Day 60. On Day 100, normal lung structure was found in all rats. The recipients of Group III showed decreased signs of AR in the early course, however, severe CR was found on Day 60 and Day 100. Extensive airway inflammation with destruction of the subepithelial layer of the smaller airways resulted in severe early obliterative bronchiolitis.


CONCLUSIONS
Untreated severe AR in the early course after lung transplantation results in CR in the F344-to-WKY model. Preventive treatment with MP during the early phase of AR clearly diminishes the degree of AR and the graft recovers completely without any evidence of CR. Late application of steroids during the zenith of AR is successful to control the extent of AR, however, it fails to prevent CR.
Department of Cardiovascular Surgery, Kiel University Hospital, Germany.
S W
SW
Hirt
X M
XM
You
F
F
Möller
K
K
Boeke
M
M
Starke
U
U
Spranger
H U
HU
Wottge
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D008775:Methylprednisolone