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Immunotoxicology of immunomodulators
1Laboratoire d'Immunotoxicologie Fondamentale et Clinique, INSERM U80, Lyon, France.
Immunotoxicology is the study of the immune system as a target organ for the toxicity of drugs and chemicals. As immunotoxicologists focused most of their interest on immunosuppression, the toxic consequences of immunomodulation are less clearly established. However, a number of immunopharmacologically-mediated side-effects including influenza-like symptoms, exacerbation of underlying diseases, e.g. autoimmune diseases, increase in hypersensitivity reactions against unrelated antigens and inhibition of hepatic drug metabolism have been described and may be used as a basis for further safety evaluation. Current pre-clinical assessment of immunotoxicity is usually performed in the rat during sub-chronic testing. The relevance of these protocols as far as immunomodulators are concerned is unknown. Careful attention should be paid to safety pharmacology testing, e.g. cytokine release, effects on animal models of auto-immune and hypersensitivity reactions, and hepatic drug metabolism. The role of post-marketing drug surveillance should also be emphasized. Advances in our understanding of the mechanism(s) of immunomodulation together with the development of more active immunomodulators are expected to improve the current pre-clinical safety assessment of these compounds.
Immunotoxicology is the study of the immune system as a target organ for the toxicity of drugs and chemicals. As immunotoxicologists focused most of their interest on immunosuppression, the toxic consequences of immunomodulation are less clearly established. However, a number of immunopharmacologically-mediated side-effects including influenza-like symptoms, exacerbation of underlying diseases, e.g. autoimmune diseases, increase in hypersensitivity reactions against unrelated antigens and inhibition of hepatic drug metabolism have been described and may be used as a basis for further safety evaluation. Current pre-clinical assessment of immunotoxicity is usually performed in the rat during sub-chronic testing. The relevance of these protocols as far as immunomodulators are concerned is unknown. Careful attention should be paid to safety pharmacology testing, e.g. cytokine release, effects on animal models of auto-immune and hypersensitivity reactions, and hepatic drug metabolism. The role of post-marketing drug surveillance should also be emphasized. Advances in our understanding of the mechanism(s) of immunomodulation together with the development of more active immunomodulators are expected to improve the current pre-clinical safety assessment of these compounds.