Prolongation of allograft survival with viral IL-10 transfection in a highly histoincompatible model of rat heart allograft rejection

Citation
Xj. Zu et al., Prolongation of allograft survival with viral IL-10 transfection in a highly histoincompatible model of rat heart allograft rejection, TRANSPLANT, 71(5), 2001, pp. 686-691
Citations number
32
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
TRANSPLANTATION
ISSN journal
00411337 → ACNP
Volume
71
Issue
5
Year of publication
2001
Pages
686 - 691
Database
ISI
SICI code
0041-1337(20010315)71:5<686:POASWV>2.0.ZU;2-Y
Abstract
Background. The ability to express genes with potential immunoregulatory ca pacity could reduce the immunogenicity of allografts and result in long-ter m graft survival, In this study, we examine the feasibility of transferring viral interleukin-10 (vIL-10) gene into rat hearts using adenovirus by int racoronary administration. The subsequent effects of delivered vIL-10 alone or with subtherapeutic doses of cyclosporine A (CsA) on parameters of allo graft rejection (AR) were also examined. Methods. Recombinant adenovirus vectors containing vIL-10 (Ad-vIL-10) or be ta -galactosidase (Ad-beta -gal) were derived from adenovirus type 5, vIL-1 0 expression in supernatants of transfected COS7 cell cultures and in trans fected heart allografts were examined by enzyme immunoassay (EIA) and rever se transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat hear t transplants (LEWS->ACI) were performed in five groups [group 1: no treatm ent, group 2: Ad-beta -gal, group 3: Ad-vIL-10, group 4: CsA (10 mg/kg), an d group 51 Ad-vIL-10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats. Allograft tissues were also submitted for histologica l study. Results. vIL-10 expression was shown in both transfected COS7 cells and hea rt isografts, Animals transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days, P<0.001) when compared to <beta>-gal transfecte d controls. Animals treated with a single low dose injection of CsA showed no significant prolongation of graft survival compared to controls (11.7 vs . 10.5 days). Animals treated with both vIL-10 and CsA demonstrated a syner gistic prolongation of allograft survival compared with controls and with a nimals treated with CsA or vIL-10 treatment alone (36.7 days vs. 11.7, P<0. 001 or 36.7 vs,19.6, P<0.001, respectively). Histological study showed that allografts from untreated controls exhibited extensive AR with loss of gra ft architecture by day 7 posttransplant while those from the vIL-10 group s howed less AR. The best pathological scores were seen in vIL-10 + CsA-treat ed animals. Conclusions. 1) Delivering Ad-vIL-10 into donor hearts by intracoronary per fusion results in overexpression of vIL-10 and significantly prolongs cardi ac allograft survival in a highly histoincompatible rat model. 2) Subtherap eutic doses of CsA do not prolong allograft survival, but act synergistical ly with vIL-10 to significantly prolong graft survival beyond that achieved with either agent alone.