Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft reje ction. The histological findings of chronic renal allograft rejection inclu de inflammation, vascular intimal thickening, glomerulosclerosis, tubular a trophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chr onic rejection within 60 days. During the early phase of the process in thi s model, CMV increased and prolonged the inflammatory response,the expressi on of adhesion molecules, intercellular adhesion molecule-1 and vascular ce ll adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of variou s growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which i nduce smooth muscle cell proliferation in the vascular wall and collagen sy nthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-i nfected grafts. In summary, CMV infection accelerated and enhanced the earl y immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts. Copyright (C) 2000 S. Karger AG, Basel.