The popliteal lymph node assay: a tool for predicting drug allergies

Abstract

A considerable number of drugs is able to induce systemic hypersensitivity in man. Systemic hypersensitivity can be drug- or autoantigen-specific, but in either case a complex of immunological processes and predisposing factors are involved and it is rarely if ever noticed in standard toxicity testing. The popliteal lymph node assay (PLNA) is regarded a suitable test to screen for the immunostimulating ability of a chemical, which may indicate its immunosensitizing potential. The most simple, primary PLNA measures popliteal lymph node hyperplasia after subcutaneous injection of a chemical into the footpad of the hindpaw of a mouse or rat. In order to assess the involvement of T cells, and hence immunosensitizating potential of a chemical, anamnestic immune reactions to a chemical or its metabolite can be measured in previously exposed (and sensitized) animals or in naive animals that received an adoptive transfer of syngeneic T cells from previously exposed animals. In the recently introduced modified PLNA, defined reporter antigens TNP-OVA (T cell-dependent antigen) and TNP-Ficoll (T cell-independent antigen) are used to distinguish between sensitizing and non-sensitizing (IgG1-response or not to TNP-Ficoll, respectively) and between mere inflammatory and complete innocent (no IgG1-response to TNP-Ficoll and an IgG1-response or not to TNP-OVA, respectively) drugs. Results with about 130 compounds (drugs and environmental pollutants) with the various types of the PLNA show a good correlation with documented immunostimulating (both autoimmunogenic and allergic) potential and no false negative chemicals were detected if metabolism was considered. The PLNA awaits further validation before this test can be recommended as a tool for prediction of drug allergy.