Prediction of drug allergenicity: possible use of the local lymph node assay.
The mouse local lymph node assay (LLNA) is currently used for the prospective identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. In this respect, the assay has been fully and formally evaluated and validated, and has been accepted recently as a stand-alone method for the identification of potential skin sensitizers. The assay involves topical application of test substance and the subsequent measurement of proliferative responses in the lymph nodes draining the site of exposure. The testing of new drug entities using a similar assay technique could offer a potential alternative for the identification of potential drug allergens. Currently, the popliteal lymph node assay (PLNA), or modifications of it, are used in research studies for the identification of drugs which have the potential to cause allergic or autoimmunogenic reactions. The PLNA involves subcutaneous application of test substance into the hind footpad, followed by the measurement of proliferative responses, or other parameters of immune activation, in the popliteal lymph nodes. However, these assays have not been validated systematically and the potential utility of a modified LLNA for use in the identification of such compounds is discussed.
Warbrick
E V
EV
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK. Vicky.Warbrick@syngenta.com
Dearman
R J
RJ
Kimber
I
I
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D003877:Dermatitis, Contact / Q000209:etiology* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D011237:Predictive Value of Tests