The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals — A preliminary study

Abstract

Low mol. wt compounds were tested in the popliteal lymph node (PLN) assay to study whether PLN reactivity could be related to the ability of the compounds to induce autoimmune disorders in man. PLN reactions were measured 7 days after a single subcutaneous (s.c.) injection of dissolved compounds in amounts of 0.3 – 2.0 mg into one hind footpad of mice and assessed as the weight increase of the draining PLN relative to the PLN weight of the untreated contralateral paw. Hydralazine, chlorpromazine, diphenylhydantoin, carbamazepine, phenylbutazone and nitrofurantoin, all being drugs with a documented potential to induce systematic immunological disorders in man, caused marked PLN reactions. False negative PLN responses were observed following injection of procainamide and isoniazid. Among systemic drugs without known potential to induce autoimmune reactions in humans, quinacrine, denzimol and niridazole significantly increased PLN weights, while phenobarbital, levamisole and disulfiram had no effect. Chemicals with a well-known capacity to induce contact dermatitis in man like 2,4-dinitro-1-chlorobenzene, α-methylene-γ-butyrolactone, p-phenylenediamine, 5-nitro-2-furaldehyde semicarbazone, 2-mercaptobenzothiazol and 1,3-dibutyl-2-thiourea caused marked PLN reactions, while the non-sensitizer 2,4-dichloro-1-nitrobenzene failed to do so. It is concluded that the PLN assay as applied in this study may give a rapid first indication of immunomodulating potential of low mol. wt compounds, but it does not discriminate as to the kind of immunomodulation. False negative or false positive results obtained with the PLN assay may relate to the limited opportunity for extensive metabolic conversion of drugs under these conditions, and stress that no conclusions should be drawn on the basis of PLN assay data alone.