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An intravenous exposure mouse model for prediction of potential drug‐sensitization using reporter antigens popliteal lymph node assay
Author(s) -
Lin Mingbao,
Sun Wei,
Wang Yingchao,
Li Xiang,
Jin Yecheng,
Gong Wan,
Fan Xiaohui,
Wang Yi
Publication year - 2012
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1696
Subject(s) - local lymph node assay , immune system , medicine , antigen , sensitization , immunology , lymph node , ovalbumin , antibody , drug , concanavalin a , pharmacology , lymph , chemistry , in vitro , pathology , biochemistry , skin sensitization
Immune‐mediated drug hypersensitivity is a particularly concerning health‐safety issue among clinicians given its unpredictability and potentially life‐threatening effects, especially with exposure to intravenous drugs. Therefore, the development of intravenous drug‐exposure models for drug‐hazard assessments has garnered increasing interest in recent years. In this study, we used reporter antigens popliteal lymph node assay to investigate the potential value of intravenous exposure to a selected variety of allergenic compounds, including ovalbumin (OVA), concanavalin A (ConA) and diclofenac. The trinitrophenyl (TNP)‐specific antibody‐forming cells were used to assess the systemic immune responses to a bystander antigen. Mice were subsequently sensitized by TNP–OVA, and then intravenous exposure to one of the selective compounds. As expected, all positive compounds induced significant popliteal lymph node (PLN) proliferation compared with the control. OVA significantly increased Cluster of Differentiation 4 receptors (CD 4 ) + interleukin‐4 (IL‐4) + T‐helper 2 (Th2) cells and, consequently, increased the ratios of IL‐4/interferon‐ γ (IFN‐ γ ) antibody‐forming cells (AFCs) in PLNs, while bringing about a dose‐dependent increase in immunoglobulin G1 (IgG1) AFCs; these findings indicate that a Th2 hypersensitivity response was induced. A Th2 response was also observed in diclofenac sodium‐treated groups, and for ConA, a more mixed Th1/Th2 immune response appeared to be induced. In addition, there was no marked reaction with the negative compound. Together, it seems likely that the intravenous exposure model may be useful for drug‐induced systemic hypersensitivity assessments. Copyright © 2011 John Wiley & Sons, Ltd.