Evaluation of the Immunotoxic Potential of Pharmaceuticals: Functional Aspects
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Drug Infomarion Journal, Vol. 31, pp. 1331-1336. 1997 Printed in the USA. All rights reserved.
EVALUATION OF THE IMMUNOTOXIC POTENTIAL OF PHARMACEUTICALS: FUNCTIONAL ASPECTS M. PALLARDY, PHD, C. BLOT,PHD, S. KERDINE,PHD, H. LEBREC,PHD, AND R. ROGER,PHD Immunotoxicologie, INSERM U461, Facultt de Pharmacie Paris-Sud, Chatenay-Malabry, France
P. RIEU, MD Service de Ntphrologie, HBpitaJ de Bicstre, Le Kremlin-Bicetre, France
Developing a battery of immune function assays to screen potential immunotoxic compounds has been a major issue these past years. Combining histopathology of lymphoid organs with several functional tests fosters the detection of an immunosuppressive drug and in addition provides information concerning the nonobservable adverse effect dose, thus fostering the performance of risk assessment. More work is urgently needed to carefully evaluate differences between results obtained in rodents and humans due to the origin of the cells used toperform the immune function assays, to develop more physiological tests, and to quantify the occupational risk linked to immunosuppressive molecules. The sensitization potential of a drug depends on the activation of specific lymphocyte but the clinical outcome is related to Thlflh2 differentiation and the “cytokine” background of the individual. Measuring cytokine production in “lymph node assays” will help to assess the potential of pharmaceuticals to produce contact and respiratory allergy.
Key Words: Immunotoxicology; Immunosuppression; Hypersensitivity; Pharmaceuticals
INTRODUCTION THE IMMUNE SYSTEM is now recognized as a target organ for the adverse effects of many agents including xenobiotics (drugs and chemicals). Immunotoxic molecules may lead to two main types of effects: immunosuppression which may result in an increased susceptibilityto tumors or infectious diseases or dysregulation of the immune response
Resented at the DIA Workshop “Immunotoxicity of Pharmaceuticals: Current Knowledge. Testing Strategies, Risk Evaluation & Consequences for Human Health,”October 2-4 1996, Montreux. Switzerland. Reprint address: Dr. M. Pallardy. Immunotoxicologie, INSERM U461, Facult6 de Phannacie Paris-Sud, rue JB Cltment, 92296 Chatenay-Malabry, France.
leading to hypersensitivity and autoimmunity. The term “immunity” refers to all the mechanisms used by the body as protection against environmental agents that are foreign to the body. Such immunity may be “natural” or “specific.” Natural immunity is conferred by all those elements with which an individual is born and which are always present at very short notice to protect the individual from challenges by “foreign” invaders. Among these elements are phagocytic cells including granulocytes, monocytes, and macrophages. Natural killer cells (NK) also play a role in the initial defense against neoplastically transformed and virus-infected cells, at a stage when antigen-specific cytotoxic T-lymphocytes have not yet expanded.
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M.Pallardy et al.
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