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Keywords:

  • autoimmune thyroiditis;
  • CTLA4Ig;
  • cytokine;
  • dog;
  • semi-quantitative RT-PCR;
  • T cell proliferation

Abstract

Background

The present study aimed to determine the effect of canine CTLA4Ig on canine autoimmune thyroiditis. In a previous study, we established a canine model of autoimmune thyroiditis by immunizing normal dogs with bovine thyroglobulin. An in vitro study using recombinant CTLA4Ig revealed that this protein can inhibit the expression of Th1-type cytokines and the pro-inflammatory cytokines tested.

Methods

As a result of the in vitro study, we constructed therapeutic CTLA4Ig/silica-nanoparticles and applied them to the treatment of experimentally induced canine autoimmune thyroiditis.

Results

Gene therapy resulted in significant reductions in anti-canine-thyroglobulin autoantibody titer, anti-T4 antibody titer and T-cell proliferation against thyroglobulin and in the mRNA expressions of interleukin-18 in fresh peripheral blood mononuclear cells (PBMC) from all dogs. There was also a significant reduction compared to day 0 in tumor necrosis factor-α and interferon-γ levels in the supernatant from cultured PBMC.

Conclusions

The CTLA4Ig-induced suppression of Th1 cytokines is relatively more significant than it appears because autoimmune thyroiditis is a Th1-polarized disease. Thus, CTLA4Ig can improve Th1/Th2 cytokine balance in autoimmune thyroiditis by downregulating Th1 cytokines. Copyright © 2008 John Wiley & Sons, Ltd.