Inhibitory Effect of Interferon-γon the Response of Human Thyrocytes to Thyrotropin (TSH) Stimulation: Relationship Between the Response to TSH and the Expression of DR Antigen

Abstract

Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

“…An inhibitory effect on TSH-stimulated Tg synthesis and secretion was also produced by IFN-g both in cultured human thyrocytes (48) and in FRTL-5 cells (49) ( Table 1). Similar inhibition of TSH-stimulated Tg secretion was caused by IFN-g in thyrocytes from Graves' disease patients (50).…”

Exacerbation of Thyroid Autoimmunity by Interferon .ALPHA. Treatment in Patients with Chronic Viral Hepatitis: Our Studies and Review of the Literature.

“…Although IFN~inhibi-tion of thyroid function has been well documented [40], the direct inhibitory effect of IFNa and -/3 on thyroid function is at present controversial [40^43].…”

Evidence supporting the identity in Graves' disease of thyroid-stimulating antibody and thyroid growth-promoting immunoglobulin G as assayed in FRTL5 cells.

“…Regarding correlates ofgoiter size with assay data, it is probable that more than a single bioactive substance will influence thyroid growth in an individual patient. Apart from the coexistence of TSAb and other antibodies that affect the TSH receptor (reviewed in 31), it is now recognized that y-interferon may reduce TSH-stimulated thyroid cell metabolism (32) and growth (33) in vitro. It is thus feasible that in vivo, particularly in thyroids with marked lymphocytic infiltration, such action of y-interferon might modulate the size of the goiter.…”