Generation of a mouse model of thyroid storm and preliminary investigation of the therapeutic effects of ghrelin

Autor: Chiaki Kurimoto, Yasushi Furukawa, Takashi Akamizu, Asako Doi, Ken Takeshima, Shuhei Morita, Hiroshi Iwakura, Hiroyuki Ariyasu, Hiroto Furuta, Masahiro Nishi, Taka-Aki Matsuoka
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Endocrine Disorders, Vol 24, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 1472-6823
DOI: 10.1186/s12902-024-01680-8
Popis: Abstract Background Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. Methods We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. Results Serum IL-6 was increased in patients with TS compared with those with Graves’ disease as the diseased control (18.2 vs. 2.85 pg/mL, P
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