© 1994 Oxford University Press
research-article |
Immunotoxicological Investigation Using Pharmaceutical Drugs: In Vivo Evaluation of Immune Effects
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*Laboratoire de Toxicologie INSERM CJF 93.01. Faculté de Pharmacie Paris XI, rue J. B. Clément, 92296 Chatenay Malabry, France
Département de Biologie Clinique, Institut Gustave Roussy, rue C. Desmoulins 94805 Villejuif Cedex, France
Laboratoire de Microbiologie, Faculté de Pharmacie PARIS XI, rue J. B. Clément, 92296 Chatenay Malabry, France
Received August 18, 1992; accepted December 30, 1993
Traditional methods for toxicological assessment have indicated that the immune system is a frequent target of toxic insult following subchronic or chronic exposure to xenobiotics. However, most of the xenobiotics evaluated in standardized protocols were environmental chemicals and correlation with available clinical data was not possible. The purpose of this work was to evaluate the potential immunosuppressive effects of pharmaceutical drugs using a standardized protocol developed for immunotoxicological assessment. Two groups of pharmaceutical drugs were utilized: (a) drugs without known immunosuppressive effect linked to their utilization in human therapy (cimetidine, furosemide, indomethacin, amoxicillin, and procainamide) and (b) immunosuppressive drugs (azathioprine, cyclosporine A, and dexamethasone). Ex vivo tests using B6C3F1 mice were performed after a 28-day repeat dose regimen and assessed: (a) immunopathology, (b) cell-mediated immunity, (c) humoral immunity, and (d) nonspecific immunity. Host resistance to Listeria monocytogenes was also assessed following exposure to immunosuppressive drugs. The results showed that (a) immunopathology and immune function assays were necessary to detect all immunotoxicants and (b) the effects observed with nonimmunotoxic drugs were sometimes statistically significant but the biological significance of these effects is unlikely.