Opioid Peptides Mediate the Suppressive Effect of Stress on Natural Killer Cell Cytotoxicity

Shavit, Yehuda; Lewis, James W.; Terman, Gregory W.; Gale, Robert Peter; Liebeskind, John C.

doi:10.1126/science.6691146

Cited by 605 publications

(147 citation statements)

References 49 publications

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“…If acute distress or stress can adversely affect NK activity, as recent data suggest (Aarstad et al, 1983;Herberman, 1982;Kiecolt-Glaser et al, 1984a,b;Shavit et al, 1984), then there could be poorer detection and elimination of transformed cells, contributing to the uncontrolled growth of neoplasms. Therefore, distress could potentially contribute to carcinogenesis directly (through faulty DNA repair) as well as indirectly (by affecting immune surveillance or competence) (Fox, 1981).…”

Section: Discussionmentioning

confidence: 99%

Distress and DNA repair in human lymphocytes

et al. 1985

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This research assessed differences in DNA repair in lymphocytes from highand low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high-and low-distress subgroups.The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DATA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.

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Section: Discussionmentioning

confidence: 99%

Distress and DNA repair in human lymphocytes

et al. 1985

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“…However, there are contradictory evidence from studies on enkephaline and morphine on NK cell functions. The treatment with morphine decreased NK cell activity (53,54), whereas the treatment with enkephaline increased NK cell activity or had no effect (51,52). The morphine inhibitory effect on NK cell appears not to be mediated via hypothalamic opioid system, as the morphine effect is only observed after direct administration into the periaqueductal gray matter but not after administration into different areas of the hypothalamus (55).…”

Section: Figurementioning

confidence: 92%

Chronic Ethanol Inhibits NK Cell Cytolytic Activity: Role of Opioid Peptide β-Endorphin

Boyadjieva

Dokur

Advis

et al. 2001

The Journal of Immunology

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The role of β-endorphin (β-EP) in ethanol-altered NK cell cytolytic activity is studied using male Fischer-344 rats as an animal model. Ethanol was administered for 1, 2, 3, or 4 wk in a liquid diet containing 8.7% ethanol (v/v), which means that 37% of the total calories were derived from ethanol. Rats treated with ethanol for 1 wk showed an increase in hypothalamic and plasma levels of immunoreactive (IR)-β-EP, but displayed no significant effect on NK cell activity determined by 51Cr release assay, as compared with those in pair-fed and ad libitum-fed animals. However, animals treated with ethanol for 2, 3, or 4 wk showed decreased hypothalamic and plasma levels of IR-β-EP and decreased splenic NK cell activity. No significant decrease in the number of splenocytes and NK cells or in the percentage of NK cells was seen until after 3 and 4 wk of ethanol treatment. Exposure in vitro of splenic lymphocytes obtained from control animals to various concentrations of β-EP increased NK cell activity. The opiate antagonist naltrexone blocked the β-EP-stimulated effect. The in vitro NK cell response to β-EP was reduced in the splenocytes obtained from animals treated with ethanol for 2 wk, but not in those obtained from animals treated with ethanol for 1 wk as compared with those in control animals. Additionally, β-EP administration into the paraventricular nucleus of the hypothalamus stimulated NK cell cytolytic activity, whereas the opiate blocker administration reduced NK cell activity. The NK cell responses to paraventricular nucleus β-EP were reduced in the animals treated with ethanol for 2 wk. These data provide evidence for the first time that ethanol inhibits NK cell cytolytic activity, possibly by reducing β-EP-regulated splenic NK cell function.

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“…If endogenous opioid peptides are indeed increased in AN as a result of stress or other causes, they may mediate immunosuppression (McCain et al, 1982;Shavit et al, 1984). In particular, the I FN system may be depressed as a result ofa structural similarity of IFN-a and endorphins, which may also adversely affect NK cell activity (Greening, 1984;Shavit et al, 1984Shavit et al, , 1985. Although we found increased jiendorphin plasma levels in individual AN patients, most had normal reactivity and the cases of increased /i-endorphins were not associated with lower 2-5A or CMC more than the other patients or the controls.…”

Section: Discussionmentioning

confidence: 99%

Tumour necrosis factor production and cell-mediated immunityin anorexia nervosa

Schattner

Steinbock

Tepper

et al. 1990

Clinical and Experimental Immunology

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SUMMARYFourteen patients with anorexia nervosa (AN) were studied for the production of tumour necrosis factor (TNF), the activation ofthe interferon (IFN) system and cell-mediated cytotoxicity (CMC) and the results were compared with 16 age-matched healthy women. AN patients had significantly increased spontaneous TNF production by peripheral blood mononuclear cells (PBMC) in vitro (16 + 5 tJ/ml uc' /.vw.v 4 + 3 U/ml in the control group; P<005), although no TNF was detectable in the plasma from cither group, TNF production in vilro, following stimulation of PBMC by phytohaemagglutinin (PHA) or tumour cells, was similar in AN patients and controls; however, lipopolysaeeharide (LPS) indueed TNF produetion was found to be lower in AN (f

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Opioid Peptides Mediate the Suppressive Effect of Stress on Natural Killer Cell Cytotoxicity

Cited by 605 publications

References 49 publications

Distress and DNA repair in human lymphocytes

Distress and DNA repair in human lymphocytes

Chronic Ethanol Inhibits NK Cell Cytolytic Activity: Role of Opioid Peptide β-Endorphin

Tumour necrosis factor production and cell-mediated immunityin anorexia nervosa

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