Clinical Approach to Immunotoxicology and Autoimmunity
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Drug Information Journal, Vol. 31, pp. 137S1378, 1997 Printed in h e USA. All rights reserved.
CLINICAL APPROACH TO IMMUNOTOXICOLOGY AND AUTOIMMUNITY K. WHALEY,MD, PHD, FRCP, FRCPATH Department of Microbiology and Immunology, University of Leicester, Leicester, United Kingdom
Drug-induced alterations in the immune system include immunosuppression, autoimmunity, and hypersensitivity. This paper focuses mainly on drug-induced autoimmunity. The main drug-induced organ-specific and nonorgan specific autoimmune diseases are described as are the clinical and laboratory features which are important in diagnosis. A number of factors which predispose people to the development of drug-induced autoimmune diseases have been identified, but the precise mechanisms underlying these diseases are unknown. Key Words: Immunotoxicology; Autoimmunity; Pharmaceuticals; Predisposing factors
INTRODUCTION XENOBIOTICS CAN AFFECT the immune system in a number of ways and produce three main types of effect: immunosuppression, hypersensitivity reactions, and autoimmunity. Suppression of antibody production, complement activation, or phagocyte mechanisms result in an increased susceptibility to infections, particularly with the encapsulated bacteria, Streptococcus pneumoniae, Haemophilus influenzae Type B, and meningococcus. Suppression of cell-mediated immunity as occurs in AIDS and other T cell deficiencies results in susceptibility to infections with fungi, pneumocystis carinii, viruses, and mycobacteria. Although most of these infections occur at mucosal surfaces which are in con-
Presented at the DIA Workshop “Immunotoxicity of Pharmaceuticals: Current Knowledge, Testing Strategies, Risk Evaluation, and Consequences for Human Health,’’ October 2 4 , 1996. Montreux. Switzerland. Reprint address: Dr. K. Whaley, Department of Microbiology and Immunology, University of Leicester, Leicester, United Kingdom.
tact with the environment, severe systemic infections such as septicaemia and meningitis can occur. Hypersensitivity reactions are classically divided into four groups, based on the GellCoomb’s classification. Type I (immediate) hypersensitivity is IgE-mediated and results in the clinical picture of hay fever, asthma, and anaphylaxis. Type I1 (cytotoxic) reactions are mediated by IgG or IgM antibodies and include blood transfusion reactions, autoimmune haemolytic anaemia, and thrombocytopaenia. A modified form of Type I1 reactions occurs in patients with thyrotoxicosis and myasthenia gravis in which autoantibodies to cell membrane receptors modulate cell function to produce disease. Anti-basement membrane disease (Goodpasture’s syndrome) is another example of Type I1 hypersensitivity in which the autoantibody recognizes an epitope on the glomerular a n d or pulmonary basement membrane and produces inflammation. Type I11 hypersensitivity reactions are mediated by antigen-antibody complexes either being precipitated locally in the tissues (Arthus Reaction, eg,
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