Cg. Duarte et al., The effect of the antithyroid drug propylthiouracil on the alternative pathway of complement in rats, INT J IMMUN, 22(1), 2000, pp. 25-33
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.