Anaphylaxis models in the guinea-pig

Abstract

Immediate hypersensitivity (or anaphylactic) reactions can be caused by large molecules which are directly immunogenic or by smaller molecules which bind to macromolecular carriers and act as haptens. To reproduce these reactions in animals, either systemic or local models are used in actively or passively sensitized animals, respectively. Several attempts have been made to detect the potential of new drugs and chemicals to induce anaphylactic reactions. Protocols using the inhalation of reactive low-molecular-weight compounds produced clinical symptoms in the guinea-pig. An intralaboratory validation study was initiated using a panel of six positive and one negative model compounds in a guinea-pig model combining systemic and local anaphylaxis. Anaphylactic reactions to positive model compounds were obtained only when the molecular weight was approximately 3000 or more. Overall, published results indicate that the potential to induce immediate hypersensitivity reactions can be detected as far as large-molecular-weight molecules are concerned--in contrast to the majority of low-molecular-weight drugs and chemicals.