IMMUNOTOXICOLOGICAL INVESTIGATION USING PHARMACEUTICAL DRUGS - IN-VIVO EVALUATION OF IMMUNE EFFECTS

Traditional methods for toxicological assessment have indicated that t he immune system is a frequent target of toxic insult following subchr onic or chronic exposure to xenobiotics. However, most of the xenobiot ics evaluated in standardized protocols were environmental chemicals a nd correlation with available clinical data was not possible. The purp ose of this work was to evaluate the potential immunosuppressive effec ts of pharmaceutical drugs using a standardized protocol developed for immunotoxicological assessment. Two groups of pharmaceutical drugs we re utilized: (a) drugs without known immunosuppressive effect linked t o their utilization in human therapy (cimetidine, furosemide, indometh acin, 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 asse ssed: (a) immunopathology, (b) cell-mediated immunity, (c) humoral imm unity, and (d) nonspecific immunity. Host resistance to Listeria monoc ytogenes was also assessed following exposure to immunosuppressive dru gs. The results showed that (a) immunopathology and immune function as says were necessary to detect all immunotoxicants and (b) the effects observed with nonimmunotoxic drugs were sometimes statistically signif icant but the biological significance of these effects is unlikely. (C ) 1994 Society of Toxicology.