IMMUNOTOXICITY TESTING IN THE RAT - AN IMPROVED MULTIPLE ASSAY MODEL

Improvements have been made in the multiple assay model for assessing immunotoxicity in the rat which were previously reported (Exon, J. H., Koller, L. D., Talcott, P. A., O'Reilly, C. A. & Henningsen, G. M. (1986). Immunotoxicity testing: an economical multiple-assay approach. Fund. appl. Toxic., 7, 387-397.). This improved model differs from the original in that: (1) the use of Freund's adjuvant has been eliminated from the antigen treatment schedule; (2) the same antigen, keyhole limpet hemocyanin (KHL), is used to induce both the delayed-type hypersensitivity (DTH) and specific antibody responses instead of separate antigens for each; and (3) the timing of antigen injections have been adjusted so that the DTH response is measured at the same time other assays are performed. These modifications have thus reduced the chance of non-specific stimulation of the immune system by Freund's adjuvant and eliminated possible antigen competition by using a single antigen to induce antibody synthesis and a DTH reaction. In addition, all immunoassays, including the DTH reaction, are performed at the same time, which allows for better comparison between responses and improves application to short-term repeated dose studies. Also, the immune parameters measured were shown to be sensitive to known immunosuppressants, cyclophosphamide and dexamethasone. © 1990.