ADENOVIRUS-MEDIATED INTERLEUKIN-10 GENE-TRANSFER INHIBITS POSTTRANSPLANT FIBROUS AIRWAY OBLITERATION IN AN ANIMAL-MODEL OF BRONCHIOLITIS OBLITERANS

Bronchiolitis obliterans, a form of chronic allograft rejection charac terized by progressive fibrous obliteration of the airways, is the maj or obstacle limiting prolonged survival of lung transplant recipients, To date, no effective therapy against this fatal complication exists, Interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cy tokine, inhibits various T cell and antigen-presenting cell functions, We examined the effect of IL-10 in an animal model for bronchiolitis obliterans, A heterotopic tracheal transplant model was used, IL-10 wa s administered to the recipient either in its recombinant form by osmo tic minipump or by adenoviral-mediated IL-10 gene transfer (Ad5E1mIL-1 0). Successful gene transfection and expression was confirmed by measu ring circulating IL-10 protein, Tracheal allografts were assessed hist ologically based on a scoring system, IL-10 administration (in recombi nant form or by gene transfer) inhibited the development of fibrous ai rway obliteration 3 weeks after transplantation in comparison to untre ated controls (p < 0.05), This was demonstrated only if the delivery w as initiated 5 days after transplantation and not if it was started at the time of transplantation. A single administration of the gene cons truct was sufficient to achieve the desired effect, We have shown that IL-10 can prevent the development of airway fibro-obliteration in thi s model, Gene transfection at a site distant from a graft can be used to produce a desired effect on the graft, IL-10 may be of major import ance in the control of post-transplant bronchiolitis obliterans, The t iming of its administration is critical and further studies are requir ed to determine the mechanisms underlying the observed effects of IL-1 0.