The Effect of IL-6 Neutralization on Corneal Allograft Survival

Abstract

Purpose: : Interleukin-6 (IL-6) has emerged as a critical regulator of T-helper 17 (Th17)/T regulatory (Treg) balance. In the presence of TGF-β, IL-6 inhibits Treg differentiation, favoring the development of the Th17 lineage. Utilizing a murine model of penetrating keratoplasty, we investigated the effect of IL-6 neutralization on corneal allograft survival.

Methods: : Fully disparate corneal grafts from 8-week C57BL/6 male donor mice were orthotopically transplanted into age and gender matched BALB/c recipient mice (n=10). In order to characterize the presence of IL-6 post transplantation, the expression of IL-6 in corneal allografts was quantified. Recipient mice were injected via the intraperitoneal route with anti-IL-6 or isotype antibodies daily up to day 7, and subsequently on alternate days. Survival was assessed using a clinical scoring system examining graft opacity.

Results: : Real-time PCR was performed to quantify the mRNA expression of IL-6 and IL-17 in accepted and rejected allografts at week 3. A 800-fold increase in mRNA levels of IL-6 was detected in rejected allografts compared to accepted allografts. Similarly, over a 9- fold difference in the mRNA expression of IL-17 was observed in rejected grafts. Graft survival was evaluated up to week 4 in anti-IL-6 antibody and isotype treated groups. Transplanted mice at week 4 demonstrated 80% graft survival compared with 40% in the control group.

Conclusions: : Our data shows up-regulation of both IL-6 and IL-17 in rejected allografts and prolonged graft survival following IL-6 neutralization.

Keywords: transplantation • cornea: basic science • immunomodulation/immunoregulation