Abstract
At the time we began our investigations of the modulation of immune function and tumor development by neural and endocrine opioid systems, several findings suggested that this was a reasonable avenue to explore. For example, focal electrical stimulation of an opioid-rich brain region was found to increase tumor growth (Brechner et al., 1983; Simon et al., 1980), specific brain lesions alter immune functions (Cross et al., 1982; Stein et al., 1982), and immune responses have been correlated with changes in brain neural activity (Besedovsky et al., 1983). Also, evidence was accumulating from in vitro studies that opioids influence the functioning of the immune system (for reviews see Plotnikoff and Miller, 1983; Weber and Pert, 1984). It was our intent to use environmental stressors as stimuli for activating endogenous opioid systems and observe their effects on tumor development and immune competence. Examination of the literature pertaining to the effects of stress on these processes, however, presented us with a somewhat confusing picture. This literature contained a host of seemingly contradictory results: stress can either enhance, suppress, or not affect tumor development or immune function (e.g. Jensen, 1968; Newberry and Sengbush, 1979; Nieburgs et al., 1977; Riley, 1981; Sklar and Anisman, 1981).
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References
Akil, H., Madden, J., Patrick, R.L., and Barchas, J.D., 1976, Stress-induced increase in endogenous opiate peptides; concurrent analgesia and its partial reversal by naloxone, in: “Opiates and Endogenous Opioid Peptides”, H.W. Kosterlitz, ed., Elsevier, Amsterdam.
Akil, H., Shiomi, H., and Matthews, J., 1985, Induction of the intermediate pituitary by stress: Synthesis and release of a nonopioid form of ß-endorphin. Science, 227: 424–426.
Besedovsky, H., Del Re, A., Sorkin, E., Da Prada, M., Burri, R., and Honegger, C., 1983, The immune response evokes changes in brain noradrenergic neurons. Science, 221: 564–566.
Bogden, A.E., Taylor, D.J., Kuo, E.Y.H., Mason, M.M., and Speropoulos, A., 1974, The effect of perphesazine-induced serum prolactin reponse on estrogen primed mammary tumor-host systems, 13762 and R-35 mammary adenocarcinoma. Cancer Res., 34: 3018–3025.
Brechner, T., Motyka, D., and Sherman, J.E., 1983, Growth enhancement of a prolactin-sensitive mammary tumor by periaqueductal gray stimulation. Life Sci., 32: 525–530.
Brown, S.M., Stimmel, B., Taub, R.N., Kochwa, S., and Rosenfield, R.E., 1974, Immunologic dysfunction in heroin addicts. Arch. Intern. Med., 134: 1001–1006.
Chang, K.-J., 1984, Opioid peptides have actions on the immune system. TINS, 7: 234–235.
Cherubin, C.E. and Brown, J., 1968, Systemic infection in heroin addicts. Lancet, 1: 298–299.
Cherubin, C.E. and Millian, S.J., 1968, Serologic investingations in narcotic addicts I. Ann. Intern. Med., 69: 739–742.
Cross, R.J., Brooks, W.H., Roszman, T.L., and Markesbery, W.R., 1982, Hypothalamic-immune interactions: effect of hypophysectomy on neuroimmunomodulation. J. Neurol. Sci., 53: 557–566.
Faith, R.E., Liang, H.J., Murgo, A.J., and Plotnikoff, N.P., 1984, Neuroimmunomodulation with enkephalins: Enhancement of human natural killer (NK) cell activity in vitro. Clin. Immun. Immunopath., 31: 412–418.
Froelich, C.J., and Bankhurst, A.D., 1984, The effect of ß-endorphin on natural killer cytotoxicity and antibody dependent cellular cytotoxicity. Life Sci., 35: 261–265.
Gilman, S.C., Schwartz, J.M., Milner, R.J., Bloom, F.E., and Feldman, J.D., 1982, ß-endorphin enhances lymphocyte proliferative reponses.Proc. Natl. Acad. Sci. ( USA ), 79: 4226–4230.
Hayes, R.L., Bennett, G.J., Newlon, P.G., and Mayer, D.J., 1978, Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli. Brain Res., 155: 69–90.
Ho, W.K.K., and Leung, A., 1979, The effect of morphine addiction on concanavalin A mediated blastogenesis. Pharmacol. Res. Commun., 1: 413–419.
Herberman, R.B., and Ortaldo, J.R., 1981, Natural killer cells: Their role in defenses against disease. Science, 214: 24–30.
Jensen, M.M., 1968, Influence of stress on murine leukemia virus infection. Proc. Soc. exp. Biol. Med., 127: 610–614.
Kay, N., Allen, J., and Morley, J.E., 1984, Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity. Life Sci., 35: 53–59.
Kreider, J.W., Bartllet, G.L., Purnell, D.M., and Webb, S., 1978, Immunotherapy of an established rat mammary adenocarcinoma (13762A) with intratumor injection of Corynebacterium parvum. Cancer Res., 38: 689–692.
Laudenslager, M.L., Ryan, S.M., Drugan, R.C., Hyson, R.L., and Maier, S.F., 1983, Coping and immunosuppression: Inescapable but not escapable shock suppresses lymphocyte proliferation. Science, 221: 568–570.
Lewis, J.W., Cannon, J.T., and Liebeskind, J.C., 1980, Opioid and nonopioid mechanisms of stress analgesia. Science, 208: 623–625.
Lewis, J.W., Shavit, Y., Terman, G.W., Gale, R.P., and Liebeskind, J.C., 1983a, Stress and morphine affect survial of rats challenged with a mammary ascites tumor (MAT 13762B). Nat. Immun. Cell Growth Regul., 3: 43–50.
Lewis, J.W., Shavit, Y., Terman, G.W., Nelson, L.R., Gale, R.P., and Liebeskind, J.C., 1983b, Apparent involvement of Opioid peptides in stress-induced enhancement of tumor growth. Peptides, 4: 635–638.
Lewis, J.W., Sherman, J.E., and Liebeskind, J.C., 1981, Opioid and nonopioid stress analgesia: assessment of tolerance and cross-tolerance with morphine, J. Neurosci., 1: 358–363.
Lewis, J.W., Tordoff, M.G., Liebeskind, J.C., and Viveros, 0.H., 1982a, Evidence for adrenal medullary opioid involvement in stress analgesia. Soc. Neurosci. Abstr., 8: 778.
Lewis, J.W., Tordoff, M.G., Sherman, J.E., and Liebeskind, J.C., 1982b, Adrenal enkephalin-like peptides may mediate opioid stress analgesia. Science, 217: 557–559.
Maier, S.F. and Seligman, M.E.P., 1976, Learned helplessness: Theory and evidence. J. exp. Psychol. Gen., 105: 3–46.
Maier, S.F., Sherman, J.E., Lewis, J.W., Terman, G.W., and Liebeskind, J.C., 1983, The opioid/nonopioid nature of stress-induced analgesia and learned helplessness. J. exp. Psychol. Anim. Behay., 9: 80–90.
Martin, F.C., Shavit, Y., Terman, G.W., Pechnick, R.N., Oh, C., and Liebeskind, J.C., 1985, Stereospecificity of opiate immunosuppression in rats. Soc. Neurosci. Abstr., 11.
Mathews, P.M., Froelich, C.J., Sibbit Jr., W.L., and Bankhurst, A.D., 1983, Enhancement of natural cytoxicity by ß-endorphin. J. Immunol., 130: 1658–1662.
McCain, H.W., Lamster, I.B., Bozzone, J.M., and Grbic, J.T., 1982, ß-endorphin modulates human immune activity via non-opiate receptor mechanisms. Life Sci., 31: 1619–1624.
Newberry, B.H., and Sengbush, L., 1979, Inhibitory effects of stress on experimental mammary tumors. Cancer Detect. Prevent., 2: 225–233.
Nieburgs, H.E., Weiss, J., Navarrete, M., Grillone, G., and Siedlecki, B., 1977, Inhibitory and enhancing effects of various stress on experimental mammary tumorigenesis. Cancer Detect. Prevent., 2: 463–470.
Plotnikoff, N.P., and Miller, G.C., 1983, Enkephalins as immunomodulators. Int. J. Immunopharmac., 5: 437–441.
Ragavan, V., and Frantz, A.G., 1981, Suppression of serum prolactin by naloxone but not anti-ß-endorphin antiserum in stressed and unstressed rats. Life Sci., 28: 921–929.
Riley, V., 1981, Psychoneuroendocrine influences on immunocompetence and neoplasia. Science, 212: 1100–1109.
Shavit, Y., Depaulis, A., Terman, G.W., Martin, F.C., Gale, R.P., and Liebeskind, J.C., 1985.Fed. Proc, 44: 1489.
Shavit, Y., Lewis, J.W., Terman, G.W., Gale, R.P., and Liebeskind, J.C., 1983a, The effects of stress and morphine on immune function in rats. Soc. Neurosci. Abstr., 9: 117.
Shavit, Y., Lewis, J.W., Terman, G.W., Gale, R.P., and Liebeskind, J.C., 1983b, Endogenous opioids may mediate the effects of stress on tumor growth and immune function. Proc. West. Pharmacol. Soc., 26: 53–56.
Shavit, Y., Lewis, J.W., Terman, G.W., Gale, R.P., and Liebeskind, J.C., 1984, Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science, 223: 188–190.
Shavit, Y., Ryan, S.M., Lewis, J.W., Laudenslager, M.L., Terman, G.W., Maier, S.F., Gale, R.P., and Liebeskind, J.C., 1983c, Inescapable but not escapable stress alters immune function. The Physiologist, 26:A-64.
Shavit, Y., Terman, G.W., Martin, F.C., Gale, R.P., and Liebeskind, J.C., 1984b, Naltrexone-sensitive suppression of the immune system’s natural killer cells by morphine. Soc. Neurosci. Abstr., 10: 726.
Siegel, R.A., Chowers, I., Conforti, N., Feldman, S., and Weidenfeld, J., 1982, Effects of naloxone on basal and stress-induced ACTH and corticosterone secretion in the male rat–site and mechanism of action. Brain Res., 249: 103–109.
Simon, R.H., Lovett, E.J. III, Tomaszek, D., and Lundy, J., 1980, Electrical stimulation of the midbrain mediates metastatic tumor growth. Science, 209: 1132–1133.
Sklar, L.S., and Anisman, H., 1979, Stress and coping factors influence tumor growth. Science, 205: 513–515.
Sklar, L.S., and Anisman, H., 1981, Stress and cancer. Psychol. Bull, 89: 369–406.
Stein, M., Keller, S.E., and Schleiffer, S.J., 1982, The role of brain and the neuroendocrine system in immune regulation - potential links to neoplastic diseases. In: Biological Mediators of Behavior and Disease: Neoplasia, S. Levy, ed., Elsevier, N.Y.
Tubaro, E., Borelli, G., Croce, C., Cavallo, G., and Santiangli, C., 1983, Effect of morphine on resistance to infection. J. Infect. Dis., 148: 656–666.
Visintainer, M.A., Volpicelli, J.R., and Seligman, M.E.P., 1982, Tumor rejection in rats after inescapable or escapable shock. Science, 216: 437–439.
Weber, R.J. and Pert, C.B., 1984, Opiatergic modulation of the immune system, in: “Central and Peripheral Endorphins: Basic and Clinical Aspects”, E.E. Muller and A.R. Genazzani, eds., Raven Press, New York.
Wybran, J., 1985, Enkephalins and endorphins as modifiers of the immune system: Present and future. Fed. Proc., 44: 92–94.
Zagon, I.S., and McLaughlin, P.J., 1981, Heroin prolongs survival time and retards tumor growth in mice with neuroblastoma. Brain Res. Bull., 7: 25–32.
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Lewis, J.W., Shavit, Y., Martin, F.C., Terman, G.W., Gale, R.P., Liebeskind, J.C. (1986). Effects of Stress and Morphine on Natural Killer Cell Activity and on Mammary Tumor Development. In: Plotnikoff, N.P., Faith, R.E., Murgo, A.J., Good, R.A. (eds) Enkephalins and Endorphins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0557-4_9
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DOI: https://doi.org/10.1007/978-1-4899-0557-4_9
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