Drug-Induced Autoimmunity and Autoimmune Disease
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Drug Information Journol. Vol. 31, pp. 1307-1309, 1997 Printed in the USA. All rights reserved.
DRUG-INDUCED AUTOIMMUNITY AND AUTOIMMUNE DISEASE NORMAN TALAL,MD,
AND
HOWARDDANG,PHD
University of Texas Health Science Center at San Antonio, Department of Medicine, Divsion of Clinical Immunology, San Antonio, Texas
Autoimmunity and autoimmune disease are two different things. Autoimmunity can be physiologic (natural autoantibodies), is a normal consequence of aging, and is potentially reversible (as in drug-induced autoimmunity which disappears when the offending drug is eliminated). Autoimmune disease is a pathologic attack by a self-destructive hostile immune system for reasons unknown, although genetic, possibly viral, hormonal, and environmental factors are all involved. Autoimmune disease has been likened to a civil war in which “friendlyfire” does much of the damage. A new development in autoimmunity is its relationship to apoptosis or Programmed Cell Death (PCD).Abnormalities of PCD occur in autoimmune mice and in autoimmune patients. Autoantibodies may be produced in response to DNA and nucleoprotein fragments that arise during PCD. Over 70 drugs are capable of inducing a lupus-like syndrome with antinuclear factors, arthritis, skin rashes, and pleurisy. Autoimmunity and autoimmune disease in these patients represents a form of immunotoxicity, perhaps an immune deviation related to cytokine imbalance a d o r abnormal PCD in which the autoimmune potential that exists in all of us attains a level of serologic and clinical expression. Key Words: Autoimmunity; Atoimmune disease; Drugs; Apoptosis
INTRODUCTION AUTOIMMUNITY AND AUTOIMMUNE disease are two different things. Autoimmunity can be physiologic (natural autoantibodies), is a normal consequence of aging, and is potentially reversible (as in drug-induced autoimmunity which disappears when the offending drug is eliminated). Autoimmune disease is a pathologic attack by a self-destructive hostile immune system for reasons 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: Howard Dang, PhD, University of Texas Health Science Center at San Antonio, Department of Medicine, Divsion of Clinical Immunology, 7703 Floyd Curl Drive, San Antonio, TX 78284-7874.
unknown, although genetic, possibly viral, hormonal, and environmental factors are all involved. Autoimmune disease has been likened to a civil war in which “friendly fire” does much of the damage.
AUTOIMMUNE DISEASE AND AUTOIMMUNITY ARE DIFFERENT The protective aspect of immune defense developed over time is a consequence of Darwinian natural selection. Any ancestors whose immune system was too weak to be protective are no longer represented in the modern day gene pool. An immune system that is excellent at host defense, but also highly prone to autoimmunity, has been derived. Autoimmune diseases occupy one end of
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