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

• Published in: European journal of endocrinology Vol. 153; no. 1; pp. 41 - 48
• Main Authors: Gullu, Sevim, Emral, Rifat, Bastemir, Mehmet, Parkes, Arthur B, Lazarus, John H
• Format: Journal Article
• Language: English
• Published: Colchester European Society of Endocrinology 01-07-2005; Portland Press
• Subjects: Adult; Apoptosis - drug effects; Apoptosis - immunology; Biological and medical sciences; Clinical Studies; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; In Vitro Techniques; Lovastatin - analogs & derivatives; Lovastatin - pharmacology; Lymphocytes - drug effects; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pravastatin - pharmacology; Pyridines - pharmacology; Simvastatin - administration & dosage; Simvastatin - pharmacology; Thyroid Gland - drug effects; Thyroid Gland - physiology; Thyroid. Thyroid axis (diseases); Thyroiditis, Autoimmune - drug therapy; Thyroiditis, Autoimmune - immunology; Vertebrates: endocrinology; Endocrinopathy; Human; In vivo; Hashimoto thyroiditis; Thyroid diseases; Autoimmune disease; Statin derivative; In vitro; Lymphocyte; Endocrinology
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.1.01941

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 = 10) and normal subjects (n = 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 + cells and B lymphocytes increased whilst CD8 + 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 = 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 + (both in CD8 + and CD4 + 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.