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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Influence of methimazole on murine thyroiditis. Evidence for immunosuppression in vivo.

Thionamide drugs are immunosuppressives in vitro. To examine this action in vivo, A/J mice were immunized with human thyroglobulin (hTg) (0.5 mg intraperitoneal injections for 5 d) beginning on days 6, 24, and 43 with or without methimazole (M) (0.05%) and l-thyroxine (T4) (0.1 micrograms/ml to prevent thyroid hypertrophy) in their water supply. Groups (n = 8) were killed on days 37, 42, and 59. Spontaneous splenic IgG-secreting cells determined by Staphylococcus protein A-linked sheep erythrocytes (SRBC) via indirect plaque-forming cell (PFC) assay indicated polyclonal stimulation induced by the hTg exposure (controls = 2,285 +/- 599, hTg-only = 5,570 +/- 470 PFC per 10(6) spleen cells), but this was significantly reduced in the M plus T4-treated group (3,640 +/- 415 PFC, P = 0.05). hTg antibody was measured by specific PFC assay using hTg-linked SRBC. Anti-hTg PFC were absent in controls and were 147 +/- 41, 25 +/- 8, and 173 +/- 58 PFC per 10(6) spleen cells in the hTg-only groups on days 37, 42, and 59, respectively. Anti-hTg PFC results in the M plus T4-treated animals were significantly reduced to 0, 15 +/- 5, and 63 +/- 30 anti-hTg PFC. Histological examination revealed a marked thyroiditis in hTg-only animals and a significantly reduced degree of mononuclear cell infiltration and follicular destruction in the M plus T4-treated groups (graded 1.9 compared with 3.6 in hTg-only P = less than 0.01). Examination of IgG deposition using fluorescent anti-mouse IgG revealed a similar granular pattern and degree of staining in both immunized groups. Control animals that received concurrent T4 administration alone showed similar hTg-induced murine thyroiditis to non-T4-treated animals and could not explain the apparent immunosuppression observed. In conclusion, these data demonstrated that M reduced both the splenic immune response and the degree of thyroiditis after heterologous Tg immunization, while a quantitative difference in the circulating and intrathyroidally deposited Tg antibody was not detected.[1]


  1. Influence of methimazole on murine thyroiditis. Evidence for immunosuppression in vivo. Davies, T.F., Weiss, I., Gerber, M.A. J. Clin. Invest. (1984) [Pubmed]
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