The popliteal lymph node assay: a tool for studying the mechanisms of drug-induced autoimmune disorders

Whereas it is still impossible to predict the risk for organ-specific drug-induced autoimmune disorders in animals, a large body of evidence suggests that the popliteal lymph node assay (PLNA) in mice or rats is instrumental to predict systemic drug-induced autoimmune disorders. Metabolites may be involved instead of the parent molecules in a few instances as shown by studies using animals pretreated with enzyme inducers. Histological examination can help distinguish primary irritants, contact sensitizers and 'autoimmunogenic' compounds. That a Graft-vs-Host (GvH)-like mechanism may be involved was further substantiated by the finding that histological features of a positive PLNA response to, e.g. streptozotocin, were quite similar to those of a 'true' local GvH response. In addition, this model is expected to be useful to improve our understanding of the mechanism(s) involved in systemic autoimmune reactions by studying the profile of PLN lymphocyte subpopulations and of released cytokines.