Cytokine gene expression during the development of graft coronary artery disease in mice

Immunologic injury to heart allografts is an initial and essential event in the pathogenesis of graft coronary artery disease (GAD). A variety of cyto kines expressed in heart allografts modify both acute rejection and chronic inflammation, and could contribute to the development of GAD. The present study investigated the gene expression of interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-a, interferon (IFN)-g, and Fas lig and in chronically rejecting DBA/2-to-B10.D2 mouse heart allografts at defi ned intervals of 7, 14, 28, or 70 days after transplantation by semiquantit ative reverse transcriptase-polymerase chain reaction. GAD developed gradua lly, showing the highest value for mean intima/media ratio at day 70. Fas l igand, and the Th1 cytokines IL-2 and IFN-g, were vigorously induced in all ografts at day 7, when histology showed pronounced parenchymal rejection, a nd rapidly decreased by day 28. However, the level of mRNA expression of Th 2 cytokines, IL-6 and IL-10, and other inflammatory cytokines, INF-a and IL -1 beta, were still elevated on day 28. The persistent expression of specif ic cytokines suggests an important role in chronic inflammation. Thus, a pe rsistently high level expression of inflammatory cytokines could be associa ted with chronic inflammation in the allografts, which promotes the develop ment of GAD.