A rat model of captopril immunogenicity.

Following chronic administration of the protein-reactive sulphydryl drug captopril (CP) to rats, an IgG antibody response to CP-derived antigen was detected by ELISA in rats administered the free drug at doses of 270 mumol/kg (i.p. and i.m.) and 27 mumol/kg (i.p.). The antibody response was slow to develop, requiring three series of four daily injections at one-monthly intervals before CP-specific serum IgG was apparent. The IgG antibody recognized CP-ovalbumin but not ovalbumin, and was inhibited by CP in protein-conjugated form, and by free CP and CP-disulphide, thus confirming specificity for a CP-derived antigenic determinant. A drug-induced non-drug-specific IgG response directed against human serum albumin was also observed after chronic high dose CP treatment. No IgG anti-DNA, IgM anti-CP nor IgM anti-HSA responses were seen following chronic drug administration. These studies show that CP, like the model reactive metabolite dinitrofluorobenzene, but unlike other protein-reactive drugs such as D-penicillamine and benzylpenicillin, is immunogenic in the rat. The findings also suggest the possibility that anti-CP antibodies reported in man may be drug-induced, rather than naturally occurring.