A variety of medicinal drugs, with a molecular weight of less than 1,000 dalton, can elicit systemic hypersensitivity reactions and autoimmune disorders in susceptible individuals at low incidence. Attempts to induce autoimmune disorders with drugs in experimental animals have often been unsuccessful, but a few reproducible models of drug-induced autoimmune disease are available. The induction of autoimmune reaction is, however, highly strain-specific, both in rats and mice, and is clearly determined by the immunogenetic background. A major challenge for the development of predictive toxicity testing methods and risk assessment represents the analysis of the contribution of individual factors to the development of disease. Therefore, it will be difficult to develop assays for regulatory purposes which allow hazard identification of autoimmunity-inducing drugs.
AdamsLEHessEV.Drug-Related Lupus. Incidence, Mechanisms and Clinical Implications. Drug Saf.1991;6:431–449.
2.
KammüllerMEBloksmaNSeinenW.Autoimmunity and Toxicology. Immune Disregulation Induced by Drugs and Chemicals. In: KammüllerMEBloksmaNSeinenW, eds. Autoimmunity and Toxicology. Amsterdam: Elsevier Science Publishers; 1989:3–34.
3.
UetrechtJP.The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions. Drug Metab Rev.1992;24: 299–366.
4.
AldridgeWN.The toxic oil syndrome (TOS, 1981): from the disease towards a toxicological understanding of its chemical aetiology and mechanism. Toxicol Lett.1992;64/65:59–70.
5.
MayenoANGleichGJ.Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale. Trends Biotech.1994;12:346–352.
6.
RubinRL.Autoimmune reactions induced by procainamide and hydralazine. In: KammüllerMEBloksmaNSeinenW, eds. Autoimmunity and Toxicology.Amsterdam: Elsevier Science Publishers; 1989:119–150.
7.
KruegerGRF.The pathology of diphenylhydantoin-induced lymphoproliferative reactions in animals. In: KammüllerMEBloksmaNSeinenW, eds. Autoimmunity and Toxicology.Amsterdam: Elsevier Science Publishers; 1989:391–413.
8.
GutJChristenUFreyNKochVStofflerD.Molecular mimicry in halothane hepatitis: biochemical and structural characterization of lipoylated autoantigens. Toxicology.1995;97: 199–224.
9.
GoldmanMDruetPGleichmannE.TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunity. Immunol Today.1991;12:223–227.
10.
SinigagliaF.The molecular basis of metal recognition by T cells. J Invest Dermatol.1994;102: 398–401.
11.
JiangXKhursigaraGRubinRL.Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils. Science.1994;266: 810–813.
12.
ShoenfeldYIsenbergD.The mosaic of autoimmunity. The factors associated with autoimmune disease. In: Research Monographs in Immunology Volume 12. Amsterdam: Elsevier Science Publishers; 1989.
13.
MasonD.Genetic variation in the stress response: susceptibility to experimental allergic encephalomyelitis and' implications for human inflammatory disease. Immunol Today.1991;12: 57–60.
14.
MartinSWeltzienHU.T cell recognition of haptens, a molecular view. Int Arch Allergy Immunol.1994;104:10–16.
15.
GleichmannEVohrH-WStringerCNuyensJGleichmannH.Testing the sensitization of T cells to chemicals. From murine graft-versus- host (GVH) reactions to chemical-induced GVH-like immunological diseases. In: KammüllerMEBloksmaNSeinenW. eds. Autoimmunity and Toxicology.Amsterdam: Elsevier Science Publishers; 1989:363–390.
16.
BloksmaNde BakkerJMvan RooijenHJMPuntPSeinenWKammüllerME.Long-term treatment with 5,5-diphenylhydantoin reduces lymphadenopathy and anti-ssDNA autoantibodies in C57BL/6-lpr/lpr mice. Int J Immunopharmac.1994;16:261–268.
17.
BellSAHobbsMVRubinRL.Isotyperestricted hyperimmunity in a murine model of the toxic oil syndrome. J Immunol.1992;148: 3369–3376.
18.
KimberIDearmanRJScholesEWBasketterDA.The local lymph node assay: developments and applications. Toxicology.1994;93:13–31.
19.
VialTDescotesJ.Contact sensitization assays in guinea pigs: are they predictive of the potential for systemic allergic reactions?Toxicology.1994;93:63–75.
20.
OsterlandCK.Laboratory diagnosis and monitoring in chronic systemic autoimmune diseases. Clin Chem.1994;40(11B):2146–2153.
21.
NaparstekYPlotzPH.The role of autoantibodies in autoimmune disease. Ann Rev Immunol.1993;11:79–104.
22.
KroemerGAndreuJLGonzaloJAGutierrez-RamosJCMartinez-AC.Interleukin-2, autotolerance, and autoimmunity. Adv Immunol.1991;50:147–235.
23.
TrouttABKelsoA.Lymphokine synthesis in vivo in an acute murine graft-versus-host reaction: mRNA and protein measurements in vivo and in vitro reveal marked differences between actual and potential lymphokine production levels. Int Immunol.1993;5:399–407.
24.
AkiraSTagaTKishomotoT.Interleukin-6 in biology and medicine. Adv Immunol.1993;54:1–78.
25.
Kubicka-MuranyiMGoebelsRGoebelCUetrechtJGleichmannE.T lymphocytes ignore procainamide, but respond to its reactive metabolites in peritoneal cells: demonstration by the adoptive transfer popliteal lymph node assay. Toxicol Appl Pharmacol.1993;122:88–94.
