Immunotoxicity Testing: An Economical Multiple-Assay Approach

Immunotoxicity Testing: An Economical Multiple-Assay Approach.EXON, J.H., KOLLER, L.D., TALCOTT, P.A., O'REILLY, C.A., ANDHENNINGSEN, G.M. (1986). Fundam Appl. Toxicol. 7, 387-397. Amodel for assessing immunotoxicologic effects of chemicals anddrugs was developed in the Sprague-Dawley rat whereby multipleconcomitant immunoassays were performed in a single animal.The multiple parameters of immunity assessed in each rat includedT cell-dependent IgG antibody production, delayed hypersensitivity,natural killer cell cytotox-icity, and production of three potentimmune regulating immunocytokines: macrophage-de-rived interleukin1 and prostaglandin E2, and lymphocyte-derived interleukin 2.Splenocyte and resident peritoneal macrophage numbers were alsoquantitated and spleen and thymus weights recorded. The sensitivityof this animal model was tested by treating rats with the immune-potentiatingdrugs, NPT 15392 (erythro-9-[2-hydroxy,3-nonyl]hypoxanthine)and avridine (N, N-dioctadecyl-N', N'-bis-[2-hydroxyethyl]propanediamine,or the immune-suppressive drugs, cyclophosphamide (N, N-bis[2-chloroethyl]tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine-2-oxide)and dexamethasone. Rats treated with NPT 15392 or avridine generallyhad enhanced immune responses, while those treated with cyclophosphamideor dexamethasone had decreased immune responses. Differentialresponsiveness of various immunocyte populations within individualrats to different drugs, or to doses of the same drug, indicatesthe efficacy of measuring multiple responses within the sameanimal. The multiassay-single animal approach represents aneconomical, versatile, sensitive, and relatively comprehensiveparadigm for assessing immunotoxicologic/pharmacologic propertiesof chemicals and drugs. The approach is extremely economicalsince multiple immune responses are evaluated in each animal.The approach is versatile because it is amenable to incorporationof a variety of in vitro and in vivo assays and could be appliedto almost any species. The model is relatively comprehensivebecause major types of immune responses/immunocyte populationsand immunoregulatory pathways are tested. Finally, the modelis sensitive for detecting immunosuppression as well as immunoenhancement,as validated by the use of known immune response modifiers inthis Study.