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Jun Yamada, Su-Ning Zhu, J. Wayne Streilein, M. Reza Dana; Interleukin-1 Receptor Antagonist Therapy and Induction of Anterior Chamber–Associated Immune Deviation–Type Tolerance after Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4203-4208. doi: https://doi.org/.
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purpose. Topical treatment with interleukin 1 receptor antagonist (IL-1ra) can
promote corneal allograft survival by suppressing induction of
allodestructive immunity. The purpose of these experiments was to
determine whether IL-1ra could also promote induction of
allo-protective tolerogenic pathways, including anterior
chamber–associated immune deviation (ACAID), which has been shown to
participate in long-term survival of corneal transplants.
methods. Corneal buttons from BALB/c (syngeneic) or C57BL/6 (fully mismatched
allogeneic) mice were orthotopically grafted onto BALB/c recipients.
Topical 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 after transplantation by ear-challenging grafted hosts
with donor-derived splenocytes 1 week after SC immunization. In
separate experiments, grafted mice were treated for 4 weeks before
injecting ovalbumin (OVA) into their anterior chambers to determine
their capacity to induce antigen-specific ACAID.
results. Treatment with IL-1ra did not promote, or inhibit, induction of
donor-specific ACAID compared with vehicle-treated controls at either
the early or late time points studied. However, IL-1ra treatment after
transplantation 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 suppression of
IL-1–mediated mechanisms contributes to recovery of the anterior
segment’s immunosuppressive microenvironment at least 1 month earlier
than would otherwise be seen after corneal transplantation. However,
IL-1ra treatment 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 se. This suggests that IL-1ra
promotes graft survival almost exclusively by virtue of suppressing
inflammation and not by directly promoting tolerance or
antigen-specific regulatory pathways.
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