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.
Foster
A L
AL
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Coleman
J W
JW
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D002216:Captopril / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000974:Antibodies, Antinuclear; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010047:Ovalbumin; D002216:Captopril