Increased Levels of Serum lnterleukin-18 in Graves' Disease

Miyauchi, Shozo; Matsuura, Bunzo; Onji, Morikazu

doi:10.1089/thy.2000.10.815

Cited by 42 publications

(31 citation statements)

References 27 publications

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“…In this regard, increased serum IL-18 levels have been described in patients with Graves' disease, but not after liothyronine treatment in euthyroid individuals (28). To our knowledge, we describe here for the first time a thyroxinedependent increase in serum IL-18 levels in an in vivo human model in which autoimmunity is not involved.…”

Section: Discussionmentioning

confidence: 53%

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

Botella-Carretero

Prados²,

Manzano³

et al. 2005

eur j endocrinol

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Objective: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model. Subjects and design: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4-7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry. Results: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean^S.D., 280^122 vs 183^106 pg/ml, F ¼ 3.192, P ¼ 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368^1480 vs 2564^846 pg/ml, F ¼ 21.324, P , 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9^8.6 vs 10.5^3.6%, F ¼ 4.977, P ¼ 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively. Conclusion: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans. 153 223-230 European Journal of Endocrinology

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Section: Discussionmentioning

confidence: 53%

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

Botella-Carretero

Prados²,

Manzano³

et al. 2005

eur j endocrinol

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“…Recent research showed that methimazole moderately inhibited the synthesis of immunoglobulins including TSAb (14)(15)(16)(17)(18)(19)(20). In this study, we treated GO and GD patients with methimazole and examined the effect of the drug on the T cell subgroups, the populations of Th1 and Th2 cells, and the Th1/Th2 cell ratio in these patients.…”

Section: Discussionmentioning

confidence: 97%

CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy

Xia

Zhou²,

Liang³

et al. 2006

Int J Mol Med

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Abstract. Graves' ophthalmopathy (GO) is considered to be an organ-specific autoimmune disease. However, the pathogenesis of GO is incompletely understood at the present time.To clarify the immunological differences between newly diagnosed GO and Graves' disease (GD) without ophthalmopathy or healthy controls (HC), we examined T-cell profile and the Th1/Th2 profile cell balance in GO (n=20), GD (n=20) and HC (n=20) using flow cytometry. We also assessed the influence of methimazole on the immunocyte profiles in patients with GO and GD and analyzed the relationship of the immunologic changes with CAS, FT3, FT4, TRAb, TMA and TGA among the three investigated groups. We report in this study that: 1) The percentage of CD4 + T cells and the ratio of CD4 + /CD8 + cells were higher, but the population of CD8 + T cells was lower in both GO and GD than those of HC (P<0.05); 2) The percentage of CD8 -/IFNÁ + T cells (Th1) and the ratio of CD8 -/IFNÁ + to CD8 -/IL-4 + T cells (Th1/Th2) in GO were considerably higher as compared to those in GD and HC (P<0.05). On the contrary, the population of Th1 cells, as well as the ratio of Th1/Th2 cells, was lower in GD than that of GO and HC (P<0.05); 3) There were no significant differences in T-cell profile and the Th1/Th2 cell balance in either GO or GD patients before and after methimazole treatment; 4) There was a positive correlation of Th1 cell percentage and the Th1/Th2 cell ratio with the clinical activity score (CAS) in GO (P<0.05), whereas CAS in GO had no correlation with the T-cell profile, the percentage of Th2 cells, and TRAb (P>0.05); 5) T-cell subset and the ratio of Th1/Th2 cells did not correlate significantly with FT3, FT4, TRAb, TMA, or TGA in GO and GD (P>0.05). Finally, 6) there were no statistical differences in TRAb, TMA, and TGA between early GO and GD without ophthalmopathy (P>0.05). Collectively, these results indicate that the balance of Th1/Th2 in GO shifts to Th1 dominance and that the cellular immune responses mediated by the Th1-type CD4 + cells might play a dominant role in the pathogenesis of GO, and thus suggest that the Th1 cell percentage and the ratio of Th1/Th2 cell subsets may be potentially utilized as clinical parameters for disease activity, for monitoring the effectiveness of immunosuppressive treatment, or for developing immunospecific forms of therapy for Graves' ophthalmopathy.

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“…IL-18 is not up-regulated in patients suffering from Hashimoto's thyroiditis (29), although such patients do have elevated IFN-␥ levels (see above). In mammals, IL-18 has three main roles: to induce IFN-␥ production (30), to enhance NK cell activity (31), and to activate neutrophils (32).…”

Section: Discussionmentioning

confidence: 97%

A Role for IL-15 in Driving the Onset of Spontaneous Autoimmune Thyroiditis?

Kaiser

Rothwell

Vašíček

et al. 2002

The Journal of Immunology

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The obese strain (OS) of chickens, which suffers from spontaneous autoimmune thyroiditis, is an excellent animal model for Hashimoto’s thyroiditis and provides a unique opportunity to investigate the mechanisms underlying and driving the onset of the disease. Following recent advances in cloning chicken cytokines, we can now begin to investigate the role of cytokines in driving the lymphoid infiltration of the thyroid seen in these birds from day 7 posthatch. Using real-time quantitative RT-PCR, we characterized the expression of IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-15, and IL-18 in thyroids from OS birds and control CB line birds, both in the embryo just before hatch (embryonic day 20) and at 3 and 5 days posthatch. All of these cytokines were up-regulated compared with levels in thyroids from CB birds, at least at some time points, with some evidence for coordination of regulation, e.g., for the proinflammatory cytokines IL-1β and IL-8. Only IL-15 was up-regulated at all time points. IL-15 was also shown to be up-regulated in spleens of OS birds at embryonic day 20 and 5 days posthatch, suggesting that IL-15 is constitutively up-regulated in this line of birds. This could explain the general immune system hyperreactivity exhibited by OS chickens and may be a factor driving the lymphoid infiltration of the thyroid.

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Increased Levels of Serum lnterleukin-18 in Graves' Disease

Cited by 42 publications

References 27 publications

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy

A Role for IL-15 in Driving the Onset of Spontaneous Autoimmune Thyroiditis?

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