Immunotoxicity of Pharmaceuticals: An Introduction

Abstract

The immune-mediated side effects of pharmaceuticals include lymphomas and infectious complications related to immunosuppression and immunodepression; flu-like reactions, exacerbation of allergy to unrelated allergens, and de novo induction of autoimmunity, associated with immunoenhancement; drug-induced hypersensitivity (allergic) reactions; and finally, organ-specific or systemic autoimmune diseases. A number of pharmaceuticals have been reported to induce one or several of these immune-mediated side-effects. Even though few guidelines have been published, every effort should be paid to predicting these side effects as part of the preclinical safety assessment of new pharmaceuticals. Although they are relatively infrequent they are sometimes severe, or even life-threatening. Unexpected immunosuppression, and possibly immunoenhancement, can be best addressed by tiered protocols in rodents. Contact sensitization assays or systemic anaphylaxis models can be instrumental in several instances. Autoimmunity is at present beyond the reach of preclinical assessment. The clinical relevance of these immune-mediated side effects and the validated strategies currently available should be an incentive to assess the potential immunotoxicity of pharmaceuticals preclinically on a systematic basis.