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Immunotoxicology: suppressive and stimulatory effects of drugs and environmental chemicals on the immune system

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Abstract

The fundamental characteristic of the adaptive immune system which has evolved in the vertebrates is the ability to recognise, and subsequently destroy, “foreign”, and potentially harmful, antigens. The selective advantage which the immune system confers is the capacity to resist infectious, and possibly malignant, disease. It has been apparent for many years that individuals in whom immune function is impaired, due either to a congenital defect or to other factors such as treatment with certain immunosuppressive drugs, exhibit an increased susceptibility to infection and, in some cases, an elevated risk of developing at least some forms of malignancy. There is an increasing awareness from rodent studies that a variety of drugs and environmental chemicals have the potential to unintentionally impair components of the immune system. Risk assessment, based upon data from chemically induced changes in one or more parameters of immune function, is, however, dependent upon a knowledge of the functional reserve of the immune system. One of the objectives of the meeting from which this report derives was to examine what sources of information are available, and what experimental protocols can be employed, to permit accurate evaluation of immunological reserve. Although, under normal circumstances, the immune system selectively and specifically recognises foreign antigen, it is clear that the potential to recognise “self” is present and that in certain circumstances this potential is realised. Antibodies directed against normal tissue antigens have been shown to be associated with, and in some instances the presumptive cause of, “autoimmune” disease. There is a growing list of drugs and chemicals which are capable of eliciting autoantibodies and pathological autoimmune reactions. A second purpose of this meeting and of this report was to review the current state of knowledge regarding drug- and chemical-induced autoimmunity.

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Authors and Affiliations

  1. Division of Immunology, Medical Institute of Environmental Hygiene at the Heinrich Heine University of Düsseldorf, Auf'm Hennekamp 50, D-4000, Düsseldorf, Federal Republic of Germany

    E. Gleichmann

  2. Central Toxicology Laboratory, ICI plc, SK10 4TJ, Alderley Park, Cheshire, UK

    I. Kimber & I. F. H. Purchase

Authors
  1. E. Gleichmann
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  2. I. Kimber
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  3. I. F. H. Purchase
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This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundations Standing Committee for the European Medical Research Councils and held at the ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. Those taking part were: W. N. Aldridge (AST; Toxicology Unit, Medical Research Council Laboratories, Carshalton, UK); J. Descotes (Immunotoxicology Section, Department of Pharmacology, Alexis Carrel Medical Faculty, Lyon, France); P. Druet (Groupe de Recherches sur la Pathologie Rénale et Vasculaire, INSERM U28, Hôpital Broussais, Paris, France); S. Fossum (Anatomical Institute, University of Oslo, Oslo, Norway); E. Gleichmann (Division of Immunology, Medical Institute of Environmental Hygiene, Düsseldorf, FRG); M. Haeney (Department of Immunology, Clinical Sciences Building, Hope Hospital, Salford, UK); D. Henschler (AST; Department of Toxicology and Pharmacology, University of Würzburg, FRG); B. Holmstedt (AST; Department of Toxicology, Karolinska Institute, Stockholm, Sweden); R. W. G. Johnson (Department of Surgery, Manchester Royal Infirmary, Manchester, UK); I. Kimber (ICI Central Toxicology Laboratory; Alderley Park, Macclesfield, Cheshire, UK); R. Lauwerys (AST; Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Department for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (Laboratoire de Medecine Legale et Toxicologie Medicale, Lyon, France); G.S. Panayi (Department of Medicine, Guy's Hospital Medical School, London, UK); A. H. Penninks (Department of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, Utrecht, The Netherlands); I. F. H. Purchase (AST; ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK); B. Ryffel (Sandoz A. G., Basle, Switzerland); B. Terracini (AST; Department of Pathology and Cancer Epidemiology, University of Turin, Turin, Italy); I. Todd (Department of Immunology, Middlesex Hospital Medical School, London, UK; now Department of Immunology, University Hospital, Queen's Medical Centre, Nottingham, UK); J. G. Vos (Laboratory for Pathology, National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands); B. M. Vose (ICI Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK); J. J. Weening (Department of Pathology and Internal Medicine, University of Leiden, Leiden, The Netherlands).

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Gleichmann, E., Kimber, I. & Purchase, I.F.H. Immunotoxicology: suppressive and stimulatory effects of drugs and environmental chemicals on the immune system. Arch Toxicol 63, 257–273 (1989). https://doi.org/10.1007/BF00278639

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