Cyclophosphamide-conditioned suppression of the natural killer cell response in rats

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution resulted in a conditioned aversion to saccharin and a conditioned suppression of natural killer cell (NKC) cytotoxicity. In this study, male Sprague-Dawley rats were conditioned by pairing saccharin with 50 mg/kg CY, an immunosuppressive drug with noxious gastrointestinal side-effects. Twenty-two and 26 days later, re-exposure of conditioned animals to saccharin alone re-enlisted the immunosuppressive effects of CY when NKC cytotoxicity was measured on day 29. Although CY also suppressed spleen cell number, IgG antibody titers and interleukin 2 (IL2) production, these immune responses did not appear to be affected by the behavioral conditioning paradigm in this experiment. Unique aspects of this study include the ability to measure multiple immune responses in a single rat and the finding that previous reports of behaviorally conditioned immunosuppression can be extended to another parameter, NKC cytotoxicity. These findings could have significant implications to human medicine, especially in the area of autoimmunity and immunodeficiency, and intervention and treatment of cancer.