Inhibitory effects of antithyroid drugs on oxygen radical formation in human neutrophils

The effects of antithyroid drugs and related agents on human neutrophil function were studied. Neutrophil function was mainly assessed through oxygen radical formation as determined by chemiluminescence (CL) response, superoxide anion (O-2) generation and hydrogen peroxide production. Propylthiouracil (PTU) at a therapeutic concentration (10 micrograms/ml) inhibited CL response evoked by phorbol myristate acetate (PMA) and other stimulators. The inhibitory effect was not enhanced by pre-incubation of neutrophils with PTU and not exerted through a direct cytotoxic effect of the drug. It was not related to the kind of stimulators to evoke CL response in neutrophils either. However, the inhibitory effect disappeared when PTU was removed from the reaction mixture for CL response. PTU did not inhibit O-2 generation but markedly inhibited hydrogen peroxide production in neutrophils or activity of hydrogen peroxide in vitro. Morphologically, the unique change of cellular configuration of chemotactic neutrophils caused by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not influenced with PTU. Since hydrogen peroxide is mainly derived from O-2, these observations suggest that PTU may have a scavenger effect on hydrogen peroxide activity. Inhibition of CL response in neutrophils was also demonstrated with methimazole (MMI), thiouracil and thiourea, but not with imidazole and uracil, which suggests that their inhibitory effect on CL response in neutrophils may be closely related to the antithyroid activity.