In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto's thyroiditis.
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.
Gullu
Sevim
S
Ankara University, School of Medicine, Department of Endocrinology and Metabolic Diseases, Ibn-i Sina Hospital, 10th floor, D-Block, 06100 Sihhiye, Ankara, Turkey. gullu@medicine.ankara.edu.tr
Emral
Rifat
R
Bastemir
Mehmet
M
Parkes
Arthur B
AB
Lazarus
John H
JH
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D066298:In Vitro Techniques; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy* / Q000276:immunology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C012258:mevastatin; D008148:Lovastatin; D019821:Simvastatin; C086276:cerivastatin; D017035:Pravastatin