Lymphoproliferative response to mitogen (ConA) after treatment of rats with gentamicin and doxycyclin: relevance to human therapeutics.
Interaction of xenobiotics with the immune system may result in undesirable effects such as immunosuppression. In the future, it is probable that immunological screening tests may be required for safety evaluation of new drug candidates as an adjunct to more traditional toxicity testing. The lymphoproliferative response to mitogens has been proposed as a screening test. This test has been set up and validated in mice, but will probably have to be done in rats, the species of choice for drug safety studies. This test has been adapted to rats, using both in vivo and in vitro treatments, and used to validate drugs, including doxycyclin and gentamicin (with cyclosporin A and hydroxycortisone as controls) at the dose levels used in toxicology studies. Discrepant results obtained with doxycyclin and hydroxycortisone (effect in vitro but not in vivo) suggest that further validation studies are necessary in order to assess the reliability of this test.
Salauze
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Rhône-Poulenc Rorer S.A., Drug Safety Department, Vitry, France.
Serre
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Amelin
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D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D007166:Immunosuppressive Agents; D003208:Concanavalin A; D016572:Cyclosporine; D004318:Doxycycline; D006854:Hydrocortisone