Increased Serum Concentration of Interleukin-12 in Patients with Silent Thyroiditis and Graves' Disease

Hidaka, Yoh; Okumura, Motoshi; Fukata, Shuji; Shimaoka, Yuki; Takeoka, Keiko; Tada, His Ato; Kuma, Kanji; Amino, Nobuyuki

doi:10.1089/thy.1999.9.149

Cited by 26 publications

(18 citation statements)

References 15 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, a recent study shows that adipose tissue secretion of interleukin-6 is elevated in Graves' disease (36) even after restoration of euthyroidism. Some authors have found elevated cytokine concentrations in autoimmune hypothyroidism (37,38), as opposed to our finding of decreased MBL levels. In parallel to our findings, it has been shown that serum sIL-2R levels are positively modulated by thyroid hormone, mostly independently of thyroid autoimmunity (39 -41).…”

Section: P-valuescontrasting

confidence: 99%

Thyroid hormone increases mannan-binding lectin levels

Riis¹,

Hansen²,

Thiel³

et al. 2005

eur j endocrinol

View full text Add to dashboard Cite

Background: Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields. Methods: To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves' hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic autoimmune thyroiditis before and after L-thyroxine substitution. Results: In all hyperthyroid patients, MBL levels were increased -median (range), 1886 ng/ml (1478 -7344) -before treatment and decreased to 954 ng/ml (312 -3222) after treatment (P ¼ 0.01, paired comparison: Wilcoxon's signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312 -1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356-2488) (P ¼ 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20-457) compared with 979 ng/ml (214 -1533) after L-thyroxine substitution (P ¼ 0.03, paired comparison: Wilcoxon's signed ranks test). Conclusion: Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.

show abstract

Section: P-valuescontrasting

confidence: 99%

Thyroid hormone increases mannan-binding lectin levels

Riis¹,

Hansen²,

Thiel³

et al. 2005

eur j endocrinol

View full text Add to dashboard Cite

show abstract

“…Such a result suggests a different immunological status for euthyroid and hypothyroid HT patients, and is in agreement with the experimental evidence demonstrating an important role of Th2 cytokines in the control of the Th1-mediated autoimmune process (1, 34 -36). The fact that our hypothyroid patients were on long-term L-thyroxine treatment suggests that the immunological abnormalities described could not be caused by impairment of thyroid function, as has been suggested previously (12). In this view, the peripheral lymphocytes might express specific markers reflecting the degree of organ involvement in HT.…”

Section: Discussionsupporting

confidence: 67%

“…Furthermore, the pharmacological stimulus allows the study of cytokines that are expressed at low levels, such as IL-4 (28). Cellular immune responses have been studied in circulating (6,12,18) and infiltrating lymphocytes (6 -10) of the patients with thyroid autoimmune disease. Since in the organ-specific diseases the reliable reflection of the autoimmune state lies in the target organ, the analysis of the intra-thyroid lymphocytes is probably the best way to investigate the immunological status in the patients with thyroid autoimmunity (30).…”

Section: Discussionmentioning

confidence: 99%

Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis

Mazziotti

Sorvillo

Naclerio

et al. 2003

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8 + lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations. Design and methods: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-g (IFN-g) in phorbolmyristate acetate (PMA)-stimulated CD4 + and CD8 + lymphocytes was assayed. Moreover, the CD4 + lymphocytes were also evaluated for the intracellular expression of IL-4. Results: No significant differences in CD3 + , CD4 + and CD8 + lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4 + IFN-g + , CD4+ IL-4 + and CD8 + IFN-g + ðt-test; P # 0:001Þ cells than the control subjects. Analysing the intracellular expression of IFN-g and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4 + lymphocytes than the control subjects, without any significant modification of IFN-g expression in CD4+ and CD8 + lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-g expression in both CD4 + and CD8 + lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4 + cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects. Conclusions: Our study has demonstrated that the peripheral CD4 + and CD8 + T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.

show abstract

“…ported in patients with GD [21][22][23]. The increased expression of IL-12 mRNA in thyroid and orbital fat tissues has been reported in GD and in active GO, respectively [24,25].…”

Section: Discussionmentioning

confidence: 89%

“…IL-12 induces IL-2, IFN-γ and TNF-β from Th1 cells and IFN-γ from NK (natural killer) cells. Increased serum levels of IL-12 have been reported in GD [21][22][23]. Furthermore, IL-12B mRNA expression has been demonstrated in thyroid tissues from patients with GD [24] and in orbital fat tissues from patients with active GO [25], but not in extraocular muscle tissues (EOM), or EOM-derived T cell lines from patients with GO undergoing corrective strabismus surgery [26].…”

mentioning

confidence: 99%

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

View full text Add to dashboard Cite

Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction -restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

show abstract

Increased Serum Concentration of Interleukin-12 in Patients with Silent Thyroiditis and Graves' Disease

Cited by 26 publications

References 15 publications

Thyroid hormone increases mannan-binding lectin levels

Thyroid hormone increases mannan-binding lectin levels

Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Contact Info

Product

Resources

About