Changes of Serum Cytokines in Hyperthyroid Graves’ Disease Patients at Diagnosis and during Methimazole Treatment

Pedro, Ana B.; Romaldini, João Hamilton; Takei, Kyoko

doi:10.1159/000311519

Cited by 29 publications

(21 citation statements)

References 70 publications

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“…Under the influence of chronic antigen challenge, macrophages and CD4+ T cells can be divided into cells Th1 producing cytokines involved in the cellular response (IL-2, IFN-g, TNF-a, IL-1b), or subpopulations of Th2 lymphocytes, which secrete cytokines associated with humoral response (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 producing IL-17, IL-21, IL-22. Th3 immune cells produce mainly TGF and play an important role in protecting against the occurrence of autoimmune diseases [42][43][44]. Despite attempts to classify autoimmune thyroid disease as a classical Th1-or Th2-dependent, there is mixed Th1/Th2 immune response in both HT and in GD [16].…”

Section: Participation Of Cytokines In the Pathogenesis Of Autoimmunementioning

confidence: 99%

Rola układu immunologicznego oraz udział cytokin w patomechanizmie autoimmunologicznej choroby tarczycy (AITD)

Mikos¹,

Mikoś²,

Obara-Moszynska³

et al. 2014

Endokrynologia Polska

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Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder. AITD development occurs due to loss of immune tolerance and reactivity to thyroid autoantigens: thyroid peroxidase (TPO), thyroglobulin (TG) and thyroid stimulating hormone receptor (TSHR). This leads to infiltration of the gland by T cells and B cells that produce antibodies specific for clinical manifestations of hyperthyroidism in Graves' disease (GD) and chronic autoimmune thyroiditis (cAIT). In addition, T cells in Hashimoto's thyroiditis induce apoptosis in thyroid follicular cells, leading ultimately to the destruction of the gland. Cytokines are involved in the pathogenesis of thyroid diseases working in both the immune system and directly targeting the thyroid follicular cells. They are involved in the induction and effector phase of the immune response and inflammation, playing a key role in the pathogenesis of autoimmune thyroid disease. The presence of multiple cytokines has been demonstrated: IL-1a, IL-1b, IL-2, IL-4 , IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-a and IFN-g within the inflammatory cells and thyroid follicular cells. Finally, cytokines derived from T cells can directly damage thyroid cells, leading to functional disorders and may also stimulate the production of nitric oxide (NO) and prostaglandin (PG), thus increasing the inflammatory response in AITD. Immunological mechanisms involved in the pathogenesis of AITD are strongly related to each other, but differences in the image of cAIT and GD phenotype are possibly due to a different type of immune response observed in these two counteracting clinical thyroid diseases. This article describes the potential role of cytokines and immune mechanisms in the pathogenesis of AITD. (Endokrynol Pol 2014; 65 (2): 150-155)

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Section: Participation Of Cytokines In the Pathogenesis Of Autoimmunementioning

confidence: 99%

Rola układu immunologicznego oraz udział cytokin w patomechanizmie autoimmunologicznej choroby tarczycy (AITD)

Mikos¹,

Mikoś²,

Obara-Moszynska³

et al. 2014

Endokrynologia Polska

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“…Moreover, serum levels of IL6 are increased in hyperthyroid patients (Celik et al 1995, Pedro et al 2011. It is thus possible that excess T 3 could act systemically through circulating cytokines that can induce plasma cell differentiation.…”

Section: B220mentioning

confidence: 99%

High levels of circulating triiodothyronine induce plasma cell differentiation

Bloise

Oliveira

Nóbrega

et al. 2013

Journal of Endocrinology

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The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3 0 -triiodothyronine (T 3 ) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T 3 for 14 days. As analyzed by flow cytometry, T 3 -treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19C B-cells. T 3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220 C cells correlating with an increased percentage of CD138 C plasma cells was observed in the spleen and bone marrow of T 3 -treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulinsecreting B-cells from T 3 -treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T 3 . In conclusion, we provide evidence that high-circulating levels of T 3 stimulate plasmacytogenesis favoring an increase in plasma cells in the bone marrow, a longlived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.

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“…Os valores de IL-6 diminuíram durante o tratamento com MMI. A diminuição na concentração sérica dessas citocinas ocorreu por provável instalação do estado de eutiroidismo e pela ação anti-inflamatória e imunomoduladora do MMI (20,21).…”

Section: Discussionunclassified

“…Recentes estudos revelaram que as quimiocinas (em especial a CXCL-10) também se encontram elevadas no hipertiroidismo (20). Portanto, o aumento significativo de citocinas e quimiocinas circulantes e consequente redução de seus valores pós--restauração do eutiroidismo sugerem sua importância na imunidade da doença de Graves e, por consequên-cia, no metabolismo energético (20,21).…”

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Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol

Moretto¹,

Pedro²,

Leite³

et al. 2012

Arq Bras Endocrinol Metab

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RESUMOObjetivo: Avaliar a alteração de peso durante o tratamento do hipertiroidismo e correlacioná--la com IL-6 e TNF-alfa. Sujeitos e métodos: Quarenta e dois pacientes foram incluídos. Peso corporal (PC), índice de massa corpórea (IMC), características clínicas e laboratoriais foram registrados. IL-6 e TNF-alfa foram determinados antes do tratamento com metimazol (MMI) e no estado de eutiroidismo. Resultados: O PC foi de 59,62 ± 11,5 kg no estado de hipertiroidismo e de 69,91 ± 14,4 kg no estado de eutiroidismo (p < 0,001 Descritores Hipertiroidismo; fator de necrose tumoral alfa; interleucina-6; metimazol; hormônio tiroidiano; peso corporal ABSTRACT Objective: To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations. Subjects and methods: Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism. Results: BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m 2 to 27 kg/m 2 ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m 2 and 33.3%, BMI ≥ 25 kg/m 2 . In euthyroidism, 38% of patients had BMI < 25 kg/m 2 and 62%, BMI ≥ 25 kg/m 2 (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI. Conclusion: An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism. Arq Bras Endocrinol Metab. 2012;56(6):364-9

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Changes of Serum Cytokines in Hyperthyroid Graves’ Disease Patients at Diagnosis and during Methimazole Treatment

Cited by 29 publications

References 70 publications

Rola układu immunologicznego oraz udział cytokin w patomechanizmie autoimmunologicznej choroby tarczycy (AITD)

Rola układu immunologicznego oraz udział cytokin w patomechanizmie autoimmunologicznej choroby tarczycy (AITD)

High levels of circulating triiodothyronine induce plasma cell differentiation

Avaliação do peso corporal em pacientes com doença de Graves durante o tratamento com metimazol

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