BACKGROUNDExcessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice.

METHODSBoth NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated.

RESULTSBoth NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression.

CONCLUSIONPoly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.

Animals ; Female ; Inflammation ; chemically induced ; metabolism ; Iodine ; toxicity ; Mice ; Mice, Inbred NOD ; Poly I-C ; pharmacology ; Thyroiditis ; chemically induced ; immunology ; metabolism ; Toll-Like Receptor 3 ; metabolism

Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-alpha) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-alpha therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-alpha (pegIFN-alpha) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-alpha and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-alpha therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-alpha therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-alpha therapy and remained weakly positive after IFN-alpha therapy was discontinued.
Adult ; Antiviral Agents/*adverse effects/therapeutic use ; Female ; Graves Disease/*chemically induced ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*adverse effects/therapeutic use ; Methimazole/therapeutic use ; Propranolol/therapeutic use ; Thyroiditis/*chemically induced

Adult ; Female ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; genetics ; Mutation ; genetics ; Niacinamide ; adverse effects ; analogs & derivatives ; Phenylurea Compounds ; adverse effects ; Tandem Repeat Sequences ; genetics ; Thyroiditis ; chemically induced ; enzymology ; genetics ; fms-Like Tyrosine Kinase 3 ; genetics