Drug-specific immune responses induced by immunization with drugs in guinea pigs and mice.
In order to develop a system for evaluating the allergenicity of drugs in clinical use, we tested drugs for the ability to induce drug-specific immune responses in guinea pigs and mice. Test drugs were benzylpenicillin, procainamide, hydralazine, isoniazid, alpha-methyldopa, D-penicillamine, captopril, sulfamethoxazole and 2,4-dinitrochlorobenzene (DNCB), which are known to induce allergic responses in man including hypersensitivity reactions and drug-induced auto-immune responses. Guinea pigs were immunized with an emulsion of complete Freund's adjuvant (CFA) and 25 mg of each drug. Mice were immunized with an emulsion of CFA and 2 mg of each drug or a mixture of aluminum hydroxide gel and 2 mg of each drug. In order to examine drug-specific immune responses, we employed detection of antibodies by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis tests, active systemic anaphylaxis (ASA) tests and delayed type hypersensitivity (DTH) tests. In guinea pigs, drug-specific antibodies were detected following immunization with benzylpenicillin, procainamide, hydralazine, isoniazid, captopril, sulfamethoxazole or DNCB. Some of these drugs were also positive in DTH tests and/or ASA tests. In mice, however, only DNCB gave positive results. Therefore, our system involving immunization of guinea pigs with CFA emulsion of a drug and detection of drug-specific immune responses is considered to be an effective test method for evaluating drug allergenicity.
Katsutani
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Department of Drug Safety Research, Eisai Co., Ltd., Gifu, Japan.
Shionoya
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H
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000918:Antibody Specificity; D004342:Drug Hypersensitivity / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D005620:Freund's Adjuvant; D006168:Guinea Pigs; D006830:Hydralazine / Q000009:adverse effects*; D007538:Isoniazid / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010400:Penicillin G / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D006830:Hydralazine; D005620:Freund's Adjuvant; D010400:Penicillin G; D007538:Isoniazid