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

Mori, Keiichiro; Yoshida, Katsumi; Mihara, Masahiko; Ohsugi, Yoshiyuki; Nakagawa, Yasuaki; Hoshikawa, Saeko; Ozaki, Hiroshi; Ito, Sadayoshi

doi:10.1080/08916930802709141

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…In some mice, 100 mg/kg anti-IL-6R Ab was administered every week during OVA sensitization. The dosage of each compound was determined as previously described (12)(13)(14).…”

Section: Neutralization Studiesmentioning

confidence: 99%

Transcription Factors GATA-3 and RORγt Are Important for Determining the Phenotype of Allergic Airway Inflammation in a Murine Model of Asthma

Ano

Morishima

Ishii

et al. 2013

The Journal of Immunology

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In refractory asthma, neutrophils, rather than eosinophils, often predominate in the airways. Neutrophilic airway inflammation appears to be resistant to steroids and may be related to the Th17, rather than the Th2, cytokine milieu. However, the role of GATA-3 and RORγt, transcription factors for Th2 and Th17 cell differentiation, respectively, in the pathogenesis of steroid-insensitive asthma remains unclear. To examine the effect of GATA-3– and RORγt-overexpression backgrounds on airway inflammation and steroid sensitivity, we generated two strains of transgenic mice overexpressing GATA-3 or RORγt. Mice were sensitized and challenged with OVA. Some OVA-sensitized/challenged mice were treated with dexamethasone, anti–IL-17 Ab, CXCR2 antagonist, or anti–IL-6R Ab to demonstrate their therapeutic effects on airway inflammation. Although Ag-specific airway inflammation and hyperresponsiveness were induced in each mouse, the phenotype of inflammation showed a distinct difference that was dependent upon the genotype. GATA-3–overexpressing mice exhibited steroid-sensitive eosinophilic inflammation with goblet cell hyperplasia and mucus hyperproduction under Th2-biased conditions, and RORγt-overexpressing mice developed steroid-insensitive neutrophilic inflammation under Th17-biased conditions. The levels of keratinocyte-derived chemokine, MIP-2, IL-6, and other neutrophil chemotaxis-related mediators were significantly elevated in OVA-exposed RORγt-overexpressing mice compared with wild-type mice. Interestingly, airway hyperresponsiveness accompanied by neutrophilic airway inflammation in RORγt-overexpressing mice was effectively suppressed by anti–IL-17 Ab, CXCR2 antagonist, or anti–IL-6R Ab administration. In conclusion, our results suggest that the expression levels of GATA-3 and RORγt may be important for determining the phenotype of asthmatic airway inflammation. Furthermore, blockade of the Th17-signaling pathway may be a treatment option for steroid-insensitive asthma.

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“…In some mice, 100 mg/kg anti-IL-6R Ab was administered every week during OVA sensitization. The dosage of each compound was determined as previously described (12)(13)(14).…”

Section: Neutralization Studiesmentioning

confidence: 99%

Transcription Factors GATA-3 and RORγt Are Important for Determining the Phenotype of Allergic Airway Inflammation in a Murine Model of Asthma

Ano

Morishima

Ishii

et al. 2013

The Journal of Immunology

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The association of non-alcoholic fatty liver disease with thyroid peroxidase and thyroglobulin antibody: A new insight from SPECT-China study

et al. 2018

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Non-alcoholic fatty liver disease (NAFLD) has been studied with inflammation and immune, but the link with thyroid autoimmunity is unreported. This study aimed to explore the direct association of NAFLD with thyroid autoimmune disease (AITD) among participants with normal thyroid stimulating hormone (TSH) levels. The data were obtained from a cross-sectional study (SPECT-China). A total of 7982 participants were enrolled. Participants underwent several checkups including peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid, and liver ultrasonography (US). The prevalence of NAFLD was higher in TPOAb and/or TgAb positive [TPO/TgAb (+)] group and TPOAb and/or TgAb together with US positive [TPO/TgAb (+) and US (+)] group for both genders. After full adjustment, binary logistic analysis showed the presence of NAFLD was positively associated with the serum level of TPOAb in men (p < .001) and TgAb in women (p = .001). Both TPO/TgAb (+) and TPO/TgAb (+) and US (+) were associated with an increased risk of NAFLD in both genders [TPO/TgAb (+): odds ratio (OR) 1.474, 95% confidence interval (CI) 1.102, 1.970 in men and OR 1.308, 95%CI 1.061, 1.612 in women; TPO/TgAb (+) and US (+): OR 1.796, 95%CI 1.143, 2.820 in men and OR 1.380, 95%CI 1.058, 1.801 in women]. Thus, we got a conclusion that the prevalence of NAFLD was positively associated with the level and the positivity of TPOAb and TgAb among participants with normal TSH levels. This is the first report suggesting that there might exist common pathways in the pathogenesis of NAFLD and thyroid autoimmunity.

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The clinical role of serum concentrations of selected cytokines: IL-1β, TNF-αand IL-6 in diagnosis of autoimmune thyroid disease (AITD) in children

Mikos¹,

Mikoś

Rabska-Pietrzak³

et al. 2014

Autoimmunity

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Chronic autoimmune thyroiditis (cAIT) leads to hypothyroidism due to T cell-mediated cytotoxicity in most cases. By contrast, Graves' disease (GD) with thyrotropin receptor stimulatory autoantibodies cause hyperthyroidism. Cytokines play a crucial role in modulating immune response in both disorders. The aim of study was to evaluate the concentrations of cytokines: IL-1β, TNF-α and IL-6 in these two opposite clinical and hormonal thyroid diseases. The study group consisted of 64 children, 44 newly diagnosed, untreated children with cAIT (n = 22; with hypothyroidism) and GD (n = 22; hyperthyroidism), and the control group of 20 healthy children. Cytokine concentrations were evaluated using the ELISA technique. The studied groups of children did not differ significantly in concentrations of IL-6 (p = 0.48) and TNF-α (p = 0.067). In children with hypothyroidism, we found significantly higher concentrations of IL-1β (median 2.16 pg/ml, IQR 0.87) compared to hyperthyroidism (median 1.39 pg/l, IQR 1.27) (p < 0.01) and the control group (median 1.88 pg/ml, IQR 1.04) (p < 0.05). The results of ROC curve analysis demonstrated the usefulness of IL-1β (AUC = 0.77, p = 0.003) and TNF-α (AUC = 0.691, p = 0.034) as diagnostic parameters in cAIT which enable discrimination of children with autoimmune thyroid disease from healthy individuals. Concentrations of these markers are increased in autoimmune hypothyroidism. We found no significant sex differences in the tested parameters. In conclusion, IL-1β and TNF-α may be considered as markers of hypothyroidism, and could efficiently discriminate between healthy and autoimmune hypothyroid children. Significantly higher concentrations of IL-1β in children with hypothyroidism may be used to distinguish children with cAIT from GD patients.

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

Cited by 3 publications

References 37 publications

Transcription Factors GATA-3 and RORγt Are Important for Determining the Phenotype of Allergic Airway Inflammation in a Murine Model of Asthma

Transcription Factors GATA-3 and RORγt Are Important for Determining the Phenotype of Allergic Airway Inflammation in a Murine Model of Asthma

The association of non-alcoholic fatty liver disease with thyroid peroxidase and thyroglobulin antibody: A new insight from SPECT-China study

The clinical role of serum concentrations of selected cytokines: IL-1β, TNF-αand IL-6 in diagnosis of autoimmune thyroid disease (AITD) in children

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