Immunotoxicity testing: an economical multiple-assay approach.
A model for assessing immunotoxicologic effects of chemicals and drugs was developed in the Sprague-Dawley rat whereby multiple concomitant immunoassays were performed in a single animal. The multiple parameters of immunity assessed in each rat included T cell-dependent IgG antibody production, delayed hypersensitivity, natural killer cell cytotoxicity, and production of three potent immune regulating immunocytokines: macrophage-derived interleukin 1 and prostaglandin E2, and lymphocyte-derived interleukin 2. Splenocyte and resident peritoneal macrophage numbers were also quantitated and spleen and thymus weights recorded. The sensitivity of this animal model was tested by treating rats with the immune-potentiating drugs, 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 generally had enhanced immune responses, while those treated with cyclophosphamide or dexamethasone had decreased immune responses. Differential responsiveness of various immunocyte populations within individual rats to different drugs, or to doses of the same drug, indicates the efficacy of measuring multiple responses within the same animal. The multiassay-single animal approach represents an economical, versatile, sensitive, and relatively comprehensive paradigm for assessing immunotoxicologic/pharmacologic properties of chemicals and drugs. The approach is extremely economical since multiple immune responses are evaluated in each animal. The approach is versatile because it is amenable to incorporation of a variety of in vitro and in vivo assays and could be applied to almost any species. The model is relatively comprehensive because major types of immune responses/immunocyte populations and immunoregulatory pathways are tested. Finally, the model is sensitive for detecting immunosuppression as well as immunoenhancement, as validated by the use of known immune response modifiers in this study.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone; D064420:Drug-Related Side Effects and Adverse Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D007376:Interleukin-2; D011458:Prostaglandins E; D015232:Dinoprostone