Immunotoxicology: An overview.
Significant progress has occurred in the fields of basic and clinical immunology over the past 15 years, leading to the establishment and validation of sensitive methods for assessing immune system changes in humans as well as laboratory animals. Concern over the potential toxic effects of chemicals and certain drugs on the immune system prompted the application of these methods to assess the safety evaluation of the immune system and the establishment of the subdiscipline of immunotoxicology within toxicology. Methods have been selected and optimized for rodent testing, which have led to national and international comparative studies to demonstrate the reproducibility and utility of these methods for predicting immune system effects. Laboratories for the investigation of immunotoxicity have, likewise, been established during the past 10 years among industrial research groups for the evaluation of new chemicals and drug candidates. 6 years ago, Sterling Winthrop Inc. established an immunotoxicology laboratory dedicated to drug discovery and development effort. Experience has demonstrated that immunotoxicological assessment can represent an important aspect of any drug safety evaluation, and need not be a routine screening procedure, but should be driven by data suggestive of an immune system effect or concern over the chemical class of the agent. Assays for the evaluation are selected from a menu of validated methods on a case-by-case basis. Immunotoxicology will continue to play a more significant role in the safety and risk assessment process, because of the pivotal role of the immune system in host defence. This overview describes the structure, organization and function of the immune system, and experience with immunological methods development, application to and experience in the preclinical development of new chemical drug entities and in vitro applications.
Dean
J H
JH
Drug Development and Drug Safety Assessment, Sterling Winthrop Inc., PO Box 5000, Collegeville, PA 19426, USA.