The Potential Effect of Simvastatin on Regulatory T cells in Experimentally Induced Autoimmune Thyroiditis in Female Rats
Keywords:Autoimmune thyroiditis; Hashimoto’s Thyroiditis; Statins; pleotropic effects; simvastatin; Tregs; TGF-ß
Autoimmune thyroiditis also named Hashimoto's thyroiditis: is an inflammatory disorder of the thyroid gland. It is characterized by circulating antibodies to thyroid antigens, and enlargement of the gland with lymphocytic infiltration.
Regulatory T cells (Tregs), a particular subset of CD4+ T cells that express CD25 at a markedly increased level. they can regulate immune response in order to preserve homeostasis and self-tolerance. T cell expansion and cytokine production are restricted by Tregs. The development of this autoimmune disease is influenced by TGF-ß1 shortage. Management of HT is usually a symptomatic therapy that concentrates on HT's symptoms rather than its underlying cause. Statins, the lipid lowering medications have pleotropic effects. they can alter immunological reactions. Twenty-four female rats were used for this experiment divided into four groups (n=6), the disease was induced in all groups except group1 (control) where rats only received phosphate buffer saline, group 2 (induction group), group 3 received Prednisolone 2mg\kg orally for 30 days and group 4 received Simvastatin (4mg\kg) orally for 30 days too. Hashimoto’s thyroiditis was induced experimentally by subcutaneous injection of porcine thyroglobulin in Freund’s adjuvant emulsion (4mg/ml). Results showed an increase in Tregs and serum TGF-ß level in rats treated with simvastatin.
In conclusion, simvastatin improves the number of functioning Tregs and increases TGF-ß signaling to suppress the autoimmune reaction. Therefore, simvastatin can be a promising approach in the treatment of this disease.
- Frommer L, Kahaly GJ. Type 1 Diabetes and Autoimmune Thyroid Disease—The Genetic Link. Vol. 12, Front Endocrinol (Lausanne). 2021;12:618213.
- Cao Y, Jin X, Sun Y, Wen W. Therapeutic effect of mesenchymal stem cell on Hashimoto’s thyroiditis in a rat model by modulating Th17/Treg cell balance. Autoimmunity [Internet]. 2020;53(1):35–45.
- Weetman AP. An update on the pathogenesis of Hashimoto’s thyroiditis. J Endocrinol Invest [Internet]. 2021;44:883–90.
- Hu Y, Zhang L, Chen H, Liu X, Zheng X, Shi H, et al. Analysis of Regulatory T Cell Subsets and Their Expression of Helios and PD-1 in Patients with Hashimoto Thyroiditis. 2019 May 13;2019.
- Ralli M, Angeletti D, Fiore M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmun Rev. 2020;19(10):102649.
- Sanjabi S, Oh SA, Li MO. Regulation of the immune response by TGF-β: From conception to autoimmunity and infection. Cold Spring Harb Perspect Biol. 2017 Jun 1;9(6).
- Martinez Quintero B, Yazbeck C, Sweeney LB. Thyroiditis: Evaluation and Treatment. Am Fam Physician. 2021;104(6):609-617.
- Morofuji Y, Nakagawa S, Ujifuku K, Fujimoto T, Otsuka K, Niwa M, Tsutsumi K. Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer. Pharmaceuticals (Basel). 2022 Jan 26;15(2):151.
- Evaluation of anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line compared with doxorubicin using MTT test. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2018 Dec 15;163–9.
- Göbel A, Rauner M, Hofbauer LC, Rachner TD. Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochim Biophys Acta Rev Cancer. 2020;1873(2):188351.
- Sorathia N, George’ S, Al-Rubaye H, Zal B. Citation. European Cardiology Review [Internet]. 2019;14(2):123–32.
- Song XH, Zan RZ, Yu CH, Wang F. Effects of modified Haizao Yuhu Decoction in experimental autoimmune thyroiditis rats. J Ethnopharmacol. 2011 May 17;135(2):321–4.
- Li Y, Zuo X, Hua C, Zhao Y, Pei X, Tian M. Effects of Selenium Supplement on B Lymphocyte Activity in Experimental Autoimmune Thyroiditis Rats. Int J Endocrinol. 2021 Aug 10;2021:9439344.
- Saadoon AS, Ghazi Alabbassi M, Hameed Mohammed N. Cuscuta Chinensis potentiate the effect of methotrexate in Rheumatoid Arthritis Induced Rats. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2020 April 20(4).
- Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Roliński J. Immune disorders in Hashimoto's thyroiditis: what do we know so far?. J Immunol Res. 2015;2015:979167.
- Miyazawa K, Miyazono K. Regulation of TGF-β family signaling by inhibitory smads. Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3).
- Kim SW, Roh J, Park CS. Immunohistochemistry forPathologists: Protocols, Pitfalls, and Tips. J Pathol Transl Med. 2016 Nov;50(6):411-418.
This work is licensed under a Creative Commons Attribution 4.0 International License.