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

T. F. Davies, I. Weiss, M. A. Gerber

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38 Scopus citations

Abstract

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 μg/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 106 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 106 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 = <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.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalJournal of Clinical Investigation
Volume73
Issue number2
DOIs
StatePublished - 1984

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