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 mo rbidity and mortality after solid organ transplantation. Despite the pathol ogical and clinical changes of this disease being well-described, the etiol ogy and the causative factors are still under discussion. Several clinical, as well experimental studies, emphasize the significance of acute rejectio n. In rat model of left lung allo-transplantation (F344-to-WKY) the influen ce of acute rejection (AR) on the development of chronic rejection (CR) was studied. Methods: In Group I (n = 25) no immunosuppression was used, while methylpre dnisolone (MP) (10 mg/kg) was applied in Group II (n = 20) in the early pha se of AR on postoperative Days 9, 10, 11 and in Group III (n = 20) during A R 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 Soc iety of Heart and Lung Transplantation. Results: In Group I, AR was found at Day 15 and Day 30 which resolved spont aneously 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, sever e CR was found on Day 60 and Day 100. Extensive airway inflammation with de struction of the subepithelial layer of the smaller airways resulted in sev ere early obliterative bronchiolitis. Conclusions: Untreated severe AR in the early course after lung transplanta tion results in CR in the F344-to-WKY model. Preventive treatment with MP d uring the early phase of AR clearly diminishes the degree of AR and the gra ft recovers completely without any evidence of CR. Late application of ster oids during the zenith of AR is successful to control the extent of AR, how ever, it fails to prevent CR.