BACKGROUND: Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection. A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins. METHODS: Donor or recipient livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation. RESULTS: DA allografts given AdCMVhIL-10 24-48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of human IL-10 then decreased gradually, and human IL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL-2 and interferon-gamma were expressed without expression of IL-4 and IL-10. CONCLUSIONS: The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.
BACKGROUND:Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection. A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins. METHODS:Donor or recipient livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus vectors harboring humanIL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation. RESULTS: DA allografts given AdCMVhIL-10 24-48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of humanIL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of humanIL-10 then decreased gradually, and humanIL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL-2 and interferon-gamma were expressed without expression of IL-4 and IL-10. CONCLUSIONS: The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.
Authors: M S Bochkova; V P Timganova; K Yu Shardina; S V Uzhviyuk; N P Loginova; Ya N Troinich; S A Zamorina Journal: Bull Exp Biol Med Date: 2022-10-10 Impact factor: 0.737
Authors: F Krenzien; M Quante; T Heinbokel; M Seyda; K Minami; H Uehara; H R C Biefer; J M Schuitenmaker; S Gabardi; K Splith; M Schmelzle; A K Petrides; H Azuma; J Pratschke; X C Li; A ElKhal; S G Tullius Journal: Am J Transplant Date: 2016-11-21 Impact factor: 8.086