The popliteal lymph node (PLN) assay is based on the assumption that a
mechanism similar to a graft-versus-host (GvH) reaction is involved i
n 'GvH-like' drug-induced side-effects, including generalized lymphade
nopathy, serum sickness-like disease, scleroderma-like reaction and th
e lupus syndrome. An increased PLN weight 7-10 days after injection of
the test article into the footpad is generally held as a positive res
ponse. Most, if not all compounds reported to induce pseudo-GvH side-e
ffects in man (namely positive model compounds) have been shown to ind
uce positive PLN responses in mice and/or rats. Reproducible results h
ave been obtained in several laboratories, in some instances blindly.
However, positive responses have also been obtained with the negative
model compounds acetone and imipramine. Flow cytometry analysis and co
nventional histology failed to help differentiate between a true GvH r
esponse and a primary irritative effect. In order to confirm the poten
tial value of the PLN assay to predict the risk for drug-induced GvH-l
ike reactions, mechanistic studies are urgently needed. (C) 1997 Elsev
ier Science Ireland Ltd.