Adequate immunotoxicity testing in drug development.
Modulation of the immune system can lead to either immunostimulation or immunosuppression and can be either intended or unintended. While many effects on the immune system's components can be found as a result of a drug treatment or chemical exposure, true immunotoxicity occurs when such treatment results in adverse effects or defects in the immune response. Regulatory expectations to evaluate potential adverse effects of pharmaceuticals warrants a need for reliable and readily standardized methods. Moreover, criteria to classify a drug as an "immunotoxicant" need to be established. Examples of studies using a modified approach to measure T-cell-dependent antibody responses (the rat KLH model) and interpretation of the results in the context of immunotoxicity evaluation are discussed in this paper.
Herzyk
Danuta J
DJ
Department of Safety Assessment, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. danuta.j.herzyk@gsk.com
Gore
Elizabeth R
ER
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001379:Azathioprine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006433:Hemocyanins / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007202:Indicators and Reagents; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D018675:Toxicity Tests
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D016572:Cyclosporine; D006433:Hemocyanins; D011239:Prednisolone; C032808:keyhole-limpet hemocyanin; D001379:Azathioprine