Anti-thyroid drugs and lymphocyte function. I. The in vitro effect on blastogenesis and suppressor cell activity

The in vitro effect of the anti-thyroid drugs (ATD), propylthiouracil (PTU) and methimazole (MMI) on blastogenesis of peripheral blood mononuclear cells (PBMC) from healthy subjects was studied in 72 hr PHA stimulated cultures. PTU in therapeutic concentrations (10 micrograms/ml) suppressed blastogenesis only when added at the last 18 hr of culture, while at 100 micrograms/ml significant suppression (25%) was recorded also for PTU present throughout culture. PTU had no cytotoxic effect on Raji cells as tested by 51Cr release assay and 3H-thymidine incorporation. Moreover, strong and irreversible suppression (33%) was induced in resting PBMC on 1 hr pre-incubation with PTU. These findings and the fact that suppression was recorded only in cultures exposed to suboptimal concentration of PHA (0.5 micrograms/ml) speak against a direct anti-metabolic effect. MMI in therapeutic concentration (1 microgram/ml) and tri-iodothyronine (T3) in pharmacological concentration (10(-7)M) were much less active. Suppression of blastogenesis by PTU appeared to be mediated through suppressor cell enhancement as indicated by: (a) the augmented blastogenesis following 24 hr pre-incubation, commonly ascribed to suppressor cell depletion, was blunted by pre-incubation with PTU; (b) mixing PTU pre-treated with untreated cells reduced the expected response to PHA and (c) PTU pre-incubated, mitomycin treated cells suppressed blastogenesis of autologous or allogeneic responder cells.