Abstract
Purpose: The effect of interferon(IFN) on allograft rejection remains controversial. Some have proposed that IFNhas a protective effect on the microcirculation of allografts, while others have shown IFNto be deleterious. We investigated the effects of intracoronary IFNon cardiac rejection in a preclinical large animal model. Methods: MHC class I disparate hearts were heterotopically transplanted into swine treated with a 12-day course of cyclosporine (10-14mg/kg/day) (n 3). An Alzet osmotic mini-pump delivered IFNinto the coronary vasculature at a rate of 100ng/day. Control recipients were treated with a similar course of cyclosporine but without IFN(n 3). Results: Swine treated with IFNdeveloped an earlier onset of high grade acute rejection as compared to controls, and rejected their allografts in 19 days vs. 46 days for controls (p 0.02). Elastin staining of the cytokine treated allografts showed severe endothelialitis and intimal thickening as early as POD 13. Conclusion: The delivery of IFNinto the coronary circulation of cardiac allografts appears to accelerate both acute and chronic rejection. Targeting IFNin antirejection regimens may ameliorate both of these processes.
Published Version
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