Interleukin-1 receptor antagonist therapy and induction of anterior chamber-associated immune deviation-type tolerance after corneal transplantation

PURPOSE. Topical treatment with interleukin 1 receptor antagonist (IL-1ra) can promote corneal allograft survival by suppressing induction of allodest ructive immunity. The purpose of these experiments was to determine whether IL-1ra could also promote induction of allo-protective tolerogenic pathway s, including anterior chamber-associated immune deviation (ACAID), which ha s been shown to participate in long-term survival of corneal transplants. METHODS. Corneal buttons from BALB/c (syngeneic) or C57BL/6 (fully mismatch ed allogeneic) mice were orthotopically grafted onto BALB/c recipients. Top ical IL-1ra or vehicle alone was applied to grafts three times daily. Donor -specific ACAID was measured in allogeneic grafted mice at 4 and 8 weeks af ter transplantation by ear-challenging grafted hosts with donor-derived spl enocytes 1 week after SC immunization. In separate experiments, grafted mic e were treated for 4 weeks before injecting ovalbumin (OVA) into their ante rior chambers to determine their capacity to induce antigen-specific ACAID. RESULTS. Treatment with IL-1ra did not promote, or inhibit, induction of do nor-specific ACAID compared with vehicle-treated controls at either the ear ly or late time points studied. However, IL-1ra treatment after transplanta tion led to significantly earlier restoration of the grafted eyes' capacity for inducing ACAID to soluble antigen (OVA). CONCLUSIONS. Promotion of OVA-specific ACAID by IL-1ra suggests that suppre ssion of IL-1-mediated mechanisms contributes to recovery of the anterior s egment's immunosuppressive microenvironment at least 1 month earlier than w ould otherwise be seen after corneal transplantation. However, IL-1ra treat ment does not alter induction of donor-specific ACAID after transplantation , suggesting that its anti-inflammatory activities do not lead to an ACAID- inducing signal per sc. This suggests that IL-1ra promotes graft survival a lmost exclusively by virtue of suppressing inflammation and not by directly promoting tolerance or antigen-specific regulatory pathways.