The effect of the antithyroid drug propylthiouracil on the alternative pathway of complement in rats

The effect of propylthiouracil (PTU) on the lytic activity of complement in rat serum was investigated in vivo. Rats (180 +/- 10 g) were treated daily by gavage with PTU doses of 1-50 mg/200 g body weight for time intervals r anging from I to 30 days. Serum classical pathway (CP) and alternative path way (AP) activities were determined 24 h after the last dose. A single dose of 50 mg/200 g body weight was administered to additional groups and the a nimals were sacrificed after periods of 1-48 h. The results showed a relatively small reduction (similar to 30%) in CP acti vity, evident only in animals treated with 50 mg of PTU for three weeks. Ho wever, a clear and opposite effect of PTU, an increase in lytic activity re aching values up to 180% of controls, was observed on AP activity, This eff ect was seen at all PTU doses used, and occurred within 4 days of treatment with the highest dose. Maximum activity was observed at intermediate inter vals, depending on the PTU dose, with a return to control levels occurring after the longer periods of treatment. The lytic activity of serum from ani mals treated with a single PTU dose of 50 mg/200 g body weight and sacrific ed 1-48 h after dosing did not differ from controls. Serum levels of thyroi d hormone (triiodo L-thyronine, T3, and thyroxine, T4) were determined in r epresentative groups of treated animals (injected with 5 mg of PTU/200 g bo dy weight/day). These were either undetectable or considerably lower than t hose of controls. The serum PTU levels of these rats increased for up to 22 days, reaching values of 2-4 mu g/ml. PTU is described in the literature as a modulator of both cellular immune r esponses and antibody production. Upon complement activation fragments of c omplement components bind to immune complexes and to specific receptors on cells of the immune system. Thus, alteration in AP activity caused by PTU t reatment suggests a possible mechanism by which the drug exerts its modulat ory effect. Increased complement AP activity might affect events as antigen presentation and hence the onset and course of the immune response. (C) 20 00 International Society for Immunopharmacology. Published by Elsevier Scie nce Ltd. AU rights reserved.