Conditional Immunomodulation

Abstract

<p>Interest in central nervous-immune system interactions was inspired largely by the work on conditional immunomodulation (Ader and Cohen, 1975, 1985). Ader and Cohen (1975) reported that rats trained such that a taste cue (saccharine, SAC) predicted an injection of an immunosuppressant (cyclophosphamide, CY) subsequently exhibited a conditional immunosuppression in response to SAC alone.</p> <p>Experiments 1-3 were designed to evaluate reports of conditional immunosuppression after training with SAC and CY. Rats received either one or three training sessions in which SAC presentation was followed by CY injection. Upon reexposure to the SAC, antibody formation to sheep red blood cells was assessed. Rats which were trained with SAC and CY had antibody titers that did not differ from saline controls, which rats which SAC and CY in a nonpredictive manner had suppressed antibody titers.</p> <p>Experiments 4 and 5 assessed the effectiveness of environmental and drug state cues in signalling CY injections. In Experiments 4 and 5, the effect of training was to attenuate the unconditional immunosuppression produced by the CY.</p> <p>Experiments 6 and 7 further assessed conditioning with pentobarbital predicting CY. After conditioning, some animals were rested until the residual effects of the CY had dissipated. When reexposed to the pentobarbital after this period, these animals had antibody titers that were significantly elevated above those of animals that never received the CY. Other animals received seven pentobarbital injections during the rest period. These animals demonstrated extinction of the conditioned response.</p> <p>Experiment 8 assessed the effectivness of conditioning when the unconditional stimulus was antigenic rather than pharmacologic. After sensitization, rats received antigen injections paired with an environmental cue. Upon reexposure to the cue, trained rats had increased levels of rat mast cell protease II in their serum. As this protease is found only in mucosal mast cells, these results suggest that mucosal mast cells may be activated by a cue for antigen.</p> <p>In a final experiment, physiological correlates of conditional mast cell activity were examined. Ussing chambers were employed to assess responsivity of intestinal epithelium after exposure to a cue for antigen. Results indicated that sensitivity to in vitro antigen was altered in rats exposed to a cue for antigen. These results, and those of the previous studies, support the hypothesis that the nervous and immune systems communicate, and that this communication may be functionally important.</p>