Conditioned immunosuppression of a murine delayed type hypersensitivity response: dissociation from corticosterone elevation.
The mechanisms involved in behavioral modulation of immunity by Pavlovian conditioning have not been delineated, although an elevation in adrenocortical steroids has been invoked as an explanation. Therefore, we investigated whether or not a 4-day, murine delayed type hypersensitivity (DTH) response could be modified by a taste aversion conditioning paradigm. Mice were conditioned by the pairing of their saccharin (0.1%) drinking water (SAC) with a cyclophosphamide (CY) injection (50 mg/kg) on Day 0. Conditioned mice that were exposed on Day 3 to SAC + CY, SAC + normal saline, or water + CY exhibited significant suppression of DTH induced paw swelling when compared to nonconditioned controls. Conditioned immunosuppression was demonstrated, since the DTH response was suppressed by SAC without a concomitant reexposure to the immunosuppressant, CY. However, when dexamethasone (3 mg/kg) was used as the conditioning agent, the SAC + vehicle group showed no reduction in paw swelling. A serum corticosterone time course study was performed to examine possible involvement of glucocorticoids in conditioned immunosuppression. On Day 3, mice were sacrificed 30, 60, 90, 120 min and 24 h after reexposure to SAC or water. No significant differences in serum corticosterone levels were detected between nonconditioned controls and any conditioned group at any time point. These results demonstrate conditioned immunosuppression of a cell-mediated immune response that is not linked to a rise in glucocorticoid levels.
Roudebush
R E
RE
Department of Rheumatology Research, Eli Lilly & Co., Indianapolis, Indiana 46285.
Bryant
H U
HU
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical; D003345:Corticosterone / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology; D004327:Drinking Behavior; D004342:Drug Hypersensitivity / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D004487:Edema / Q000209:etiology / Q000276:immunology; D005528:Foot; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000503:physiopathology; D007108:Immune Tolerance / Q000502:physiology; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009325:Nausea / Q000139:chemically induced / Q000150:complications; D010853:Picryl Chloride / Q000276:immunology / Q000633:toxicity; D012439:Saccharin / Q000494:pharmacology; D013312:Stress, Physiological / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology; D013649:Taste
D003907:Dexamethasone; D003520:Cyclophosphamide; D012439:Saccharin; D003345:Corticosterone; D010853:Picryl Chloride