INFLUENCE OF METHIMAZOLE ON MURINE THYROIDITIS - EVIDENCE FOR IMMUNOSUPPRESSION INVIVO

Thionamide drugs are immunosuppressives in vitro. To examine this action in vivo, A/J mice were immunized with human thyroglobulin (hTg) (0.5 mg i.p. injections for 5 days) beginning on days 6, 24 and 43 with or without methimazole (M) (0.05%) and l-thyroxine (T4) (0.1 .mu.g/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 = 2285 .+-. 599, hTg-only = 5570 .+-. 470 PFC/106 spleen cells) but this was significantly reduced in the M plus T4-treated group (3640 .+-. 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/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. Thus, 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.