Models for Safety Testing of Immunoreactive Pharmaceuticals

Abstract

Pharmaceuticals of different molecular structure and different therapeutic classes may cause immunological reactions (immunostimulation, immunosupression or allergy) either by themselves or by acting as haptens. Also, it is known in some instances as described later in this presentation, - and as may be further supposed - that toxic effects of drugs, in themselves indetectable, may cause release of antigens that secondarily can lead to an immune response and subsequent tissue damage. The immunological reaction may not only take place in patients treated with the drug but also in experimental animals used for preclinical safety testing. The topic of the present paper concerns those pharmaceuticals which are species-specific proteins developed in order to be identical or related to human proteins or to interact with human cell membrane receptors or antigens. Since such pharmaceuticals are species-specific for humans, they may accordingly be immunoreactive in experimental animals used for safety testing and animals may lack specific ligands for these substances. Additionally there could be, as briefly mentioned above, autoantigens released due to the primary effect of the pharmaceutical, but not distinguishable as a two step reaction in conventional testing systems.