Prevention of lymphocytic thyroiditis in iodide-treated non-obese diabetic mice lacking interferon regulatory factor-1

Abstract

Objective: Interferon regulatory factor-1 (IRF-1) is a critical regulator of interferon-g (IFNg)-mediated immune responses. To determine whether IRF-1 is involved in the pathogenesis of thyroiditis in animal models, we evaluated the incidence of iodide-induced lymphocytic thyroiditis (LT) in nonobese diabetic (NOD) mice lacking IRF-1 as well as IRF-1 þ/þ and þ /2 mice. Design: IRF-1 þ /þ , þ/2 and 2 /2 NOD mice at 6 weeks of age were fed water (group 1) or iodide water (group 2) for 8 weeks. Methods: Thyroids were examined histopathologically and intrathyroidal lymphocytic infiltration was arbitrarily graded. Serum thyroxine (T 4 ) and anti-mouse thyroglobulin antibody (anti-mTgAb) levels were measured. Spleen cell population was analyzed by flow cytometry, and IFNg and interleukin-10 produced by splenocytes were measured by enzyme-linked immunosorbent assay. Results: In group 1, only 4.3% of NOD mice developed LT. In contrast, 67.6% of mice in group 2 developed the disease. Iodide treatment induced LT in more than 80% of IRF-1 þ/þ and þ/2 mice. However, no IRF-1 2 /2 mice in group 2 developed LT. There was no difference in both serum antimTgAb and T 4 levels among the three IRF-1 genotypes of NOD mice. Numbers of splenic CD8 þ T cells and IFNg production by Concanavalin A-stimulated splenocytes were markedly decreased in IRF-1-deficient NOD mice. Conclusions: IRF-1 is involved in the development of iodide-induced LT in NOD mice.

TRAIL and DR5 Promote Thyroid Follicular Cell Apoptosis in Iodine Excess-Induced Experimental Autoimmune Thyroiditis in NOD Mice

“…The extent of thyroid lymphocytic infiltration was assessed on a score of 0 to 5+, as previously reported. Briefly, a score of 0 indicates a normal thyroid, whereas 0+ indicates mild follicular changes and/or a few inflammatory cells infiltrating the thyroids; 1+ thyroiditis is defined as an infiltration of at least 125 cells in one or several follicles; 2+ represents 10-20 follicles of cellular infiltration, each the size of several follicles and involving up to one fourth of the gland; 3+ indicates that one fourth to one half of the gland is infiltrated by lymphocytes; 4+ indicates that greater than one half of the gland is destroyed; and 5+ indicates almost complete destruction of the gland with a few or no remaining follicles [37][38][39][40].…”

Effects of interleukin-6 blockade on the development of autoimmune thyroiditis in nonobese diabetic mice

“…Interferon-g (IFNg) and interleukin-10 (IL-10) levels in 48-h culture supernatants were measured using ELISA kits (Biosource International, Camarillo, CA, USA). We previously found that mouse Tg added to culture medium did not stimulate spleen cell proliferation and cytokine production in NOD mice [20,21].…”

“…Thyroiditis was induced by an 8-week iodide ingestion as previously described [20]. At the age of 6-8 weeks, mice were randomized into two groups and received tap water or 0.05% iodide water (0.64 g NaI/l).…”

“…Serum anti-mouse Tg antibody (TgAb) was measured in duplicate in one assay by a modification of an enzyme-linked immunosorbent assay (ELISA) as previously described [20,21]. In brief, 96-well microplates (Becton Dickinson and Co., Oxnard, CA, USA) were coated with mouse Tg at a concentration of 10 mg/ml in 50 mM carbonate buffer, pH 9.6, and incubated overnight at 48C.…”

Viral Hepatitis C Patients; Hypothyroidism With Relation of Interferon Treated Patients

“…23,24 In relation to interferon treated pts in different study shows that female have more hypothyroidism than male pts while in our study table-I and figure-3 shows that male have more adverse feature of hypothyroidism. 25,26 Many different study were conducted through population survey that shows that hepatitis c virus directly not involved in thyroid abnormality. 27,28,29 In my study total number of patients 117 out of them 51 (43.60%) males and 66 (56.40%) females shown figure-2.…”