GENE EXPRESSION OF VIRAL INTERLEUKIN 10 (vIL–10) PROLONGS SURVIVAL OF CORNEAL ALLOGRAFTS DEPENDING ON THE WAY OF APPLICATION

Abstract

Abstract: : Purpose: Since Th2–type cytokines may inhibit Th1–type cytokines which play an important role in allogeneic graft rejection, over–expression of Th2–type cytokines may enhance the survival of corneal allografts. In this study we investigated the immunomodulatory effect of liposome–mediated (local) and adenovirus–mediated gene transfer (systemic) of vIL–10 in an experimental keratoplasty model. Methods: Wistar–Furth (W/F) donor rat corneas (n=8) were transfected ex–vivo with liposome/DNA mixture (1µg vIL–10 plasmid+5µg LFA2000+10µg transferrin) for 3 hours at 37°C and transplanted in MHC class I/II–and mHC–antigen–disparate Lewis rats. In adenovirus group (Ad5, E1/E3 deleted, n=5), Lewis rats were treated with AdvIL–10 (1*10⁹ pfu/animal) intraperitoneally (i.p.) one day prior to be transplanted with W/F rat corneas. Results:In both groups gene transfer was successful as measured by specific ELISA. The graft’s mean survival in liposome–mediated gene therapy group was 12.0±1.0 days. Systemic administration of AdvIL–10 significantly prolonged the survival of corneal allografts. Mean survival was 15.4±3.3 days (P<0.01, compared with 9.8±0.7 days in control group treated with Adß–Gal). Conclusions: Our data indicate that systemic application by treating transplant recipient with AdvIL–10 results in a significantly prolonged survival rate for corneal allografts. The immunomodulatory effect is likely related with both local and systemic vIL–10 expression which might not be the case during local gene therapy. Further investigations will be necessary to clarify the role of vIL–10 modulatory effects on cellular immune responses. Table Survival of corneal allografts treated with vIL–10 on different routes of application  

* compared Group A with Group B

Keywords: gene transfer/gene therapy • cornea: basic science • immunomodulation/immunoregulation