The effect of interferon-gamma on rejection and neutrophil function following transplantation.
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.
Slater
A D
AD
Department of Surgery, School of Medicine, University of Louisville, KY 40292.
Klein
J B
JB
Czarniecki
C W
CW
Sonnenfeld
G
G
D000005:Abdomen; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004347:Drug Interactions; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D007371:Interferon-gamma / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D016897:Respiratory Burst / Q000187:drug effects; D016042:Transplantation, Heterotopic
D011994:Recombinant Proteins; D007371:Interferon-gamma; D016572:Cyclosporine