Outbred (namely Wistar and Sprague-Dawley) and inbred (Wistar-Furth, Lewis, Fisher 344 and Brown-Norway) strains of rats were screened for their responses to reference compounds in the popliteal lymph node (PLN) assay. Streptozotocin and diphenylhydantoin gave positive responses as evidenced by increased weight and cellularity indices in all strains used whereas procainamide, isoniazid and barbital consistently gave negative responses. Although these findings overall are in agreement with previous investigations involving these compounds, the lack of marked interstrain differences in PLN responses argues against a strong immunogenetically controlled mechanism as could be assumed in presumably auto-immune reactions. The question is raised whether drug-induced side-effects predicted by the PLN assay are basically non-autoimmune as suggested by clinical and immunological findings in man.
Get full access to this article
View all access options for this article.
References
1.
Kammüller ME, Bloksma N. & Seinen W.Autoimmunity and toxicology. Immune disregulation induced by drugs and chemicals . In: Autoimmunity and Toxicology, Kammüller ME, Bloksma N & Seinen W (eds), Amsterdam, Elsevier, 1989, pp. 3-34.
2.
Shoenfeld Y. & Isenberg D.The Mosaic of Autoimmunity (The Factors Associated with Autoimmune Disease) . Amsterdam, Elsevier, 1989.
3.
Bigazzi, PEAutoimmunity induced by chemicals. ClinicalToxicology1988; 26: 125-56.
4.
Gleichmann E. , Pals ST, Rolink, AG, Radaszkiewicz T. & Gleichmann H.Graft-versus-host reactions: clues to the etiopathology of spectrum of immunological diseases. Immunology Today1984; 5: 324-32.
5.
Ford WL, Burr W. & Simonsen M.A lymph node weight assay for the graft-versus-host activity of rat lymphoid cells. Transplantation1970; 10: 258-66.
6.
Gleichmann H.Studies on the mechanism of drug sensitization: T-cell-dependent popliteal lymph node reaction to diphenyl-hydantoin. Clinical Immunology and Immunopathology1981; 18: 203-11.
7.
Kammüller ME & Seinen W.Structural requirements for hydantoins and 2-thiohydantoins to induce lymphoproliferative popliteal lymph node reactions in the mouse. International Journal of Immunopharmacology1988; 10: 997-1010.
8.
Hurtenbach U. , Gleichmann H., Nagata N. & Gleichmann E.Immunity to D-penicillamine: genetic, cellular, and chemical requirements for induction of popliteal lymph node enlargement in the mouse. Journal ofImmunology1987; 139: 411-6.
9.
Stiller-Winkler R., Radaszkiewicz T. & Gleichmann E.Immunopathological signs in mice treated with mercury compounds-I. Identification by the popliteal lymph node assay of responder and nonresponder strains. International Journal of Immunopharmacology1988; 10: 475-84.
10.
Bloksma N., Kammüller ME, Punt P. & Seinen W.Strain dependence of primary lymph node reactions to subcutaneous injection of diphenylhydantoin in mice. In: A Toxicological Approach to Chemical-induced Autoimmunity, Kammüller's thesis, pp. 79-92, 1988.
11.
Verdier F., Virat M. & Descotes J.Applicability of the popliteal lymph node assay in the Brown-Norway rat. Immunopharmacology and Immunotoxicology1990; 12: 669-77.
12.
Gill TJ, Kunz HW, Misra DN & Cortese Hassett ALThe major histocompatibility complex of the rat. Transplantation1987; 43: 773-81.
13.
Descotes J. & Verdier F.The popliteal lymph node assay. In: Modern Methods in Immunotoxicology , Burleson G, Dean JH & Munson AE (eds). New York: Wiley-Liss, 1993; in press.
14.
Verdier F., Patriarca C., Vial T., Virat M. & Descotes J.Further validation of the popliteal lymph node (PLN) assay in the rat. Pharmacology & Toxicology1993; 73 (Suppl. II): 46.
15.
Donker AJ, Venuto RC, Vladutiu AO, Brentjens JR & Andres GAEffects of prolonged administration of D-penicillamine or captopril in various strain of rats. Brown-Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation. Clinical Immunology and Immunopathology1984; 30: 142-55.
16.
Robinson Chg , Balazs T. & Egorov IKMercuric chloride, gold sodium thiomalate, and D-penicillamine-induced antinucleolar antibodies in mice. Toxicology and Applied Pharmacology1986; 86: 159-69.
17.
Druet E., Sapin C., Fournie G., Mandet C., Günther E. & Druet P.Genetic control of susceptibility to mercury-induced immune nephritis in various strains of rat. Clinical Immunology and Immunopathology1982; 25: 203-12.
18.
Gleichmann E., Vohr HW, Stringer C., Nuyens J. & Gleichmann H.Testing the sensitization of T cells to chemicals. From murine graft-versus-host (GVH) reactions to chemical-induced GVH-like immunological diseases. In: Autoimmunity and Toxicology, Kammüller ME, Bloksma N & Seinen W (eds), Amsterdam: Elsevier, 1989, pp. 363-90.
19.
Klinkhammer C., Popowa P. & Gleichmann H.Specific immunity to streptozotocin. Cellular requirements for induction of lymphoproliferation . Diabetes1988; 37: 74-80.
20.
Krzystyniak K, BroulandJPh, Panaye G, Patriarca C, Verdier F, Descotes J & Revillard JP. Changes in CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine popliteal lymph node (PLN) test. Journal ofAutoimmunity1992; 5: 183-97.
21.
Kammüller ME , Thomas C., De Bakker JM, Bloksma N. & Seinen W.The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals-A preliminary study . International Journal of Immunopharmacology1989; 11: 293-300.
22.
Patriarca C. , Verdier F., Brouland JPh & Descotes J.Popliteal lymph node response to procainamide and isoniazid. Role of β-naphthoflavone, phenobarbitone and S9-mix pretreatment . Toxicology Letters1993; 66: 21-8.
Cardenas A. , Roels H., Bernard AM et al. Markers of early renal change induced by industrial pollutants. I. Application to workers exposed to mercury vapour . British Journal of Industrial Medicine1993 ; 50: 17-27.
