Defective Response of Natural Killer Activity to Thyroxine in Graves` Disease

Abstract

The effect of thyroxine (T4) on natural killer (NK) activity of peripheral blood lymphocytes (PBL) was investigated, using a 4-hr 51Cr release assay, in 18 patients with previously untreated Graves’ disease and in 18 controls. NK activity in patients with Graves disease was not significantly different from that in the controls. Normal T4 (NT) and high T4 (HT) medium, free T4 concentrations in which were 1.01 and 16.3 ng/dl, respectively, were used to evaluate the effect of T4 on NK activity. In the controls, NK activity increased in the NT or HT medium compared with that in the control medium at effector to target cell (E : T) ratios of 25 : 1 and 50 : 1. NK activity in the Graves’ disease patients, however, did not increase when either the NT or HT medium was used at E : T ratios of 25 : 1 and 50 : 1. These results suggest that patients with Graves’ disease have a similar NK activity to the controls but have a defect in the peripheral blood lymphocytes to increase NK activity in response to T4.

Thyroid Hormone Action on Innate Immunity

“…A positive correlation between serum T3 concentration and NK cell activity in healthy elderly subjects was recorded but exogenous T3 administration increased NK cell activity only in old individuals who had T3 concentrations at the lower end of the reference range (37). Although NK cell functionality was impaired in Graves' patients and restored in the euthyroid state (38, 39), in vitro treatment with T4 to peripheral blood lymphocytes from these patients did not show any increase in NK cell activity (40). In agreement, hyperthyroxinemia induced in mice reduced NK cell capacity to lyse target cells (41) whereas exogenous T4 or T3 administered to mice increased NK cell lytic activity (42), as well as during protein starvation (43), or aging (44).…”

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

“…Figure 1B illustrates the hypothesis that in case of dysfunctional impairment, NK cells lose their ability to protect from the development of GD. Other studies (115,117,119,120,122,131,132), with some exceptions (116,118) generally agreed on the impairment of NK activity in GD and reported that restoration of euthyroidism by antithyroid drug treatment (especially propylthiouracil) could improve NK functionality (133,134).…”

“…Several studies investigated the potential contribution of NKs in the development and/or progression of GD, but results are still inconclusive and sometimes conflicting. Table 1 reports the available data on this issue (111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123). Researchers from Osaka University observed that the total percentage of LGL, including NK-like cells, was decreased in untreated GD patients compared to euthyroid GD patients on antithyroid drug therapy and to controls; in addition, the proportion of LGL was inversely correlated to T4 and T3 levels (110)(111)(112)123).…”