In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto’s thyroiditis

Abstract

Background: Statins have apoptotic effects on many cell types. Hashimoto's thyroiditis (HT) is an autoimmune disease in which cell-mediated autoimmune mechanisms are pathogenetically involved. Objective: The aim of this study was to evaluate the in vivo effects of Simvastatin on thyroid function, lymphocyte subtypes and also to investigate the apoptotic effects of Simvastatin, Mevastatin, Pravastatin and Cerivastatin on lymphocytes from patients with HT. Methods: In the first part of the study, 11 patients with HT and subclinical hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks. Ten patients with SH and HT served as the control group. No treatment was given to controls. Thyroid function, C-reactive protein (CRP) levels and lymphocyte subtypes of both groups were determined before the study and after 8 weeks. In the second part of the study, the apoptotic effects of statins on lymphocytes were evaluated in patients with HT (n ¼ 10) and normal subjects (n ¼ 10) in vitro. Apoptosis was investigated by using Annexin-V and propidium iodide. Lymphocytes from patients and controls were incubated with different concentrations of Simvastatin, Cerivastatin, Mevastatin and Pravastatin. Results: An increase in serum free tri-iodothyronine and free thyroxine levels and a decrease in TSH levels were observed (P , 0.05) with Simvastatin treatment. CD4 þ cells and B lymphocytes increased whilst CD8 þ cells, natural killer cells and activated T lymphocytes decreased significantly in the treatment group (P , 0.05). The CRP level of the group also decreased with Simvastatin but it did not reach significance (P ¼ 0.057). None of parameters was found to be different from the baseline in the control group. In in vitro experiments, apoptosis was observed in CD3 þ (both in CD8 þ and CD4 þ cells) with all statins in both patient and control samples. Mevalonate, which was used in experiments, reversed apoptosis in some but not all samples. Conclusions:The results of this study suggested that Simvastatin is an immune modulatory agent and improves thyroid function in patients with HT. This effect is probably mediated via lymphocyte apoptosis as demonstrated with in vitro experiments and is not confined to Simvastatin since Mevastatin, Pravastatin and Cerivastatin also induced apoptosis in lymphocytes.

Different Effects of Fenofibrate on Metabolic and Cardiovascular Risk Factors in Mixed Dyslipidemic Women With Normal Thyroid Function and Subclinical Hypothyroidism

“…Simvastatin treatment of patients with subclinical hypothyroidism secondary to autoimmune thyroid disease led to a reduction of TSH levels, which was accompanied by an increase in free thyroid hormones . The authors of the study explained this effect by immunosuppressive and proapoptopic properties of statins.…”

Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia

“…It may be more ideal to survey the prevalence of hypothyroidism in the population of untreated hypercholesterolemia. After we determined the study design, a study showing that treatment with statins, in particular Simvastatin, may influence thyroid function in patients with Hashimoto thyroiditis was published [44]. Two patients were being treated with Atorvastatin among the patients of overt hypothyroidism with Hashimoto thyroiditis and 4 were being treated with Atorvastatin among the patients of subclinical hypothyroidism with Hashimoto thyroiditis.…”

Thyroid hormones: a potential ally to LDL-cholesterol-lowering agents

“…50,51 Statins are likely to have an immune-modulatory role in thyroid autoimmunity, as in vivo and in vitro studies showed an increase in serum FT3, FT4, and concomitantly a reduction in TSH levels, while CD4+ cells and B lymphocytes rose and CD8+ cells, natural killer cells and activated T lymphocytes significantly diminished. 52 According to the authors, these results are mediated by activation of apoptosis by the statins. These findings were indirectly corroborated by another study using high-dose statin therapy and reporting a significant reduction of thyroid peroxidase antibodies (TPoAB) and a decline in thyroglobulin antibodies (TgAB) in women with Hashimoto thyroiditis.…”