Abstract
In this study, we investigated the immune alterations induced in rats by an aversive conditioned stimulus that had been developed through pairings with electric shock. The results showed that the conditioned stimulus induced a pronounced suppression of the mitogenic responsiveness of splenic and blood lymphocytes and a reduction in splenic natural killer cell activity. In contrast, the conditioned stimulus did not induce any alteration in the mitogenic responsiveness of lymphocytes from the mesenteric lymph nodes. The reduction in the mitogenic responsiveness of splenic lymphocytes was not related to a reduction in the level of interleukin-2 (IL-2) production, as splenic lymphocytes from subjects exposed to the conditioned stimulus showed normal levels of IL-2. Plasma corticosterone measurements showed that glucocorticoid secretion was related to the alteration of the mitogenic responsiveness of blood lymphocytes. However, plasma corticosterone levels were not related to any of the other immune measures. These findings establish that a signal for an aversive event can have a pronounced effect on immune function, but that such an effect is dependent on the particular compartment of the immune system studied. These results support the claim that glucocorticoids can induce immune alterations, but they suggest that additional pathways must be involved in the immune alterations induced by a conditioned aversive stimulus.
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Arora, P. K., Hanna, E. E., Paul, S. M., & Skolnick, P. (1987). Suppression of the immune response by benzodiazepine receptor inverse agonists. Journal of Neuroimmunology, 15, 1–9.
Bassett, J. R., Cairncross, K. D., & King, M. G. (1973). Parameters of novelty, shock predictability, and response contingency in corticosterone release in the rat. Physiology & Behavior, 10, 901–907.
Crabtree, G. R., Munck, A., & Smith, K. A. (1980). Glucocorticoids and lymphocytes: II. Cell cycle-dependent changes in glucocorticoid receptor content. Journal of Immunology, 125, 13–17.
Cunnick, J. E., Lysle, D. T., Armfield, A., & Rabin, B. S. (1988). Shock-induced modulation of lymphocyte responsiveness and natural killer activity: Differential mechanisms of induction. Brain, Behavior, & Immunity, 2, 102–113.
Estes, W. K., & Skinner, B. F. (1941). Some quantitative properties of anxiety. Journal of Experimental Psychology, 29, 390–400.
Friedman, S. B., & Ader, R. (1967). Adrenocortical response to novelty and noxious stimulation. Neuroendocrinology, 2, 209–212.
Friedman, S. B., Ader, R., Grota, L. J., & Larson, T. (1967). Plasma corticosterone response to parameters of electric shock stimulation in the rat. Psychosomatic Medicine, 29, 323–328.
Irwin, J., & Livnat, S. (1987). Behavioral influences on the immune system: Stress and conditioning. Progress in Neuropsychopharmacology and Biological Psychiatry, 11, 137–143.
Johnson, L. K., Longenecker, J. P., Bacter, J. D., Dallman, M. F., Widmaier, E. P., & Eberhardt, N. L. (1982). Glucocorticoid action: A mechanism involving nuclear and non-nuclear pathways. British Journal of Immunology, 107, 6–23.
Keller, S. E., Weiss, J. M., Schleifer, S. J., Miller, N. E., & Stein, M. (1981). Suppression of immunity by stress: Effect of a graded series of stressors on lymphocyte stimulation in the rat. Science, 213, 1397–1400.
Keller, S. E., Weiss, J. M., Schleifer, S. J., Miller, N. E., & Stein, M. (1983). Stress-induced suppression of immunity in adrenalectomized rats. Science, 111, 1301–1304.
Laudenslager, M. L., Ryan, S. M., Drugan, R. C, Hyson, R. L., & Maier, S. F. (1983). Coping and immunosuppression: Inescapable but not escapable shock suppresses lymphocyte proliferation. Science, 111, 568–570.
Levine, S., & Treiman, D. M. (1964). Differential plasma corticosterone response to stress in four inbred strains of mice. Endocrinology, 75, 142–144.
Lewis, J. W., Shavit, Y., Terman, G. W., Gale, R. P., & Liebeskind, J. C. (1983–1984). Stress and morphine affect survival of rats challenged with a mammary ascites tumor (MAT 13762B). Natural Immunity & Cell Growth Regulation, 3, 43–50.
Lewis, J. W., Shavit, Y., Terman, G. W., Nelson, L. R., Gale, R. P., & Liebeskind, J. C. (1983). Apparent involvement of opioid peptides in stress-induced enhancement of tumor growth. Peptides, 4, 635–638.
Lysle, D. T., Cunnick, J. E., Fowler, H., & Rabin, B. S. (1988). Pavlovian conditioning of shock-induced suppression of lymphocyte reactivity: Acquisition, extinction, and preexposure effects. Life Sciences, 42, 2185–2194.
Lysle, D. T., Cunnick, J. E., Wu, R., Caggiula, A. R., Wood, P. G., & Rabin, B. S. (1988). 2-deoxy-D-glucose modulation of T-lymphocyte reactivity: Differential effects on lymphoid compartments. Brain, Behavior, & Immunity, 2, 212–221.
Lysle, D. T., Lyte, M., Fowler, H., & Rabin, B. S. (1987). Shockinduced modulation of lymphocyte reactivity: Suppression, habituation, and recovery. Life Sciences, 41, 1805–1814.
Miller, N. E. (1948). Studies in fear as an acquirable drive: I. Fear as motivation and fear reduction as reinforcement in the learning of new responses. Journal of Experimental Psychology, 38, 89–101.
Murphy, B. E. (1967). Some studies on the protein binding of steroids and their application to the routine micro and ultra-micro measurement of various steroids in body fluids by competitive protein-binding radioassay. Journal of Clinical Endocrinology, 12, 973–990.
Onsrud, M., & Thorsby, E. (1981). Influence of in vivo hydrocortisone of some human blood lymphocyte subpopulations: I. Effect of natural killer cell activity. Scandinavian Journal of Immunology, 13, 573–579.
Petitto, J. M., Skolnick, P., & Arora, P. K. (1989). Suppression of natural killer cell activity by FG 7142, a benzodiazepine receptor “inverse agonist”. Brain, Behavior, & Immunity, 3, 39–46.
Pross, H. F., & Maroun, J. A. (1984). The standardization of NK cell assays for use in studies of biological response modifiers. Journal of Immunological Methods, 68, 235–249.
Rescorla, R. A., & Lolordo, V. M. (1965). Inhibition of avoidance behavior. Journal of Comparative & Physiological Psychology, 59, 406–412.
Robbins, D. L., & Gershwin, M. E. (1978). Identification and characterization of lymphocyte subpopulations. Seminars in Arthritis & Rheumatism, 7, 245-277.
Shavit, Y., Lewis, J. W., Terman, G. W., Gale, R. P., & Liebeskind, J. C. (1984). Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science, 223, 188–190.
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This work was supported by grants from the National Institute of Mental Health (MH46284 to Donald T. Lysle, MH43411 to Bruce S. Rabin, and MH24115 to Harry Fowler)
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Lysle, D.T., Cunnick, J.E., Kucinski, B.J. et al. Characterization of immune alterations induced by a conditioned aversive stimulus. Psychobiology 18, 220–226 (1990). https://doi.org/10.3758/BF03327230
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DOI: https://doi.org/10.3758/BF03327230