Decreasing TNF-alpha results in less fibrosis and earlier resolution of granulomatous experimental autoimmune thyroiditis.

Journal: Journal Of Leukocyte Biology
Published:
Abstract

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced in DBA/1 mice by adoptive transfer of mouse thyroglobulin (MTg)-primed spleen cells. TNF-alpha is an important proinflammatory cytokine and apoptotic molecule involved in many autoimmune diseases. To study its role in G-EAT, anti-TNF-alpha mAb was given to recipient mice. Disease severity was comparable between mice with or without anti-TNF-alpha treatment at days 19-21, the time of maximal severity of G-EAT, suggesting TNF-alpha is not essential for development of thyroid inflammation. However, thyroid lesions resolved at day 48 in anti-TNF-alpha-treated mice, while thyroids of rat Ig-treated controls had fibrosis. These results suggested that reducing TNF-alpha contributed to resolution of inflammation and inhibited fibrosis. Gene and protein expression of inflammatory molecules was examined by RT-PCR and immunostaining, and apoptosis was detected using TUNEL staining and an apoptosis kit. Thyroids of anti-TNF-alpha-treated controls had reduced proinflammatory and profibrotic molecules, e.g., IFN-gamma, IL-1beta, IL-17, inducible NOS and MCP-1, at day 19 compared with thyroids of rat Ig-treated mice. There were more apoptotic thyrocytes in rat Ig-treated controls than in anti-TNF-alpha-treated mice. The site of expression of the anti-apoptotic molecule FLIP also differed between rat Ig-treated and anti-TNF-alpha-treated mice. FLIP was predominantly expressed by inflammatory cells of rat Ig-treated mice and by thyrocytes of anti-TNF-alpha-treated mice. These results suggest that anti-TNF-alpha may regulate expression of proinflammatory cytokines and apoptosis in thyroids, resulting in less inflammation, earlier resolution, and reduced fibrosis.

Authors
Kemin Chen, Yongzhong Wei, Gordon Sharp, Helen Braley Mullen
Relevant Conditions

Subacute Thyroiditis