Rats were used as a model for a living heterotopic cardiac allograft organ transplant. Rats treated in this model with recombinant rat interferon-gamma (IFN-gamma) showed accelerated rejection in a dose-dependent fashion. However, rats treated with maintenance doses of cyclosporine and IFN-gamma expressed increased rejection at 20 days that had resolved completely by 45 days post-transplantation. Polymorphonuclear leukocytes (neutrophils) were isolated from the blood of rats, and their function was determined by treating the cells with f-Met-Leu-Phe (fMLP) and measuring superoxide produced. Results indicate that the neutrophils from rats treated with maintenance doses of cyclosporine and IFN-gamma still had increased IFN-gamma-modulated fMLP-induced respiratory burst and that maintenance cyclosporine therapy can inhibit the IFN-gamma-mediated accelerated rejection without compromising the antimicrobial effects of IFN-gamma treatment.
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