Major Depressive Disorder, Alcoholism, and Reduced Natural Killer Cell Cytotoxicity

Irwin, Michael R.; Caldwell, Cindy; Smith, Tom L.; Brown, Sandra L.; Schuckit, Marc A.; Gillin, J. Christian

doi:10.1001/archpsyc.1990.01810200021003

Cited by 159 publications

(53 citation statements)

References 51 publications

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“…In other studies, sober chronic alcoholics who were well nourished and free of underlying diseases had no demonstrable abnormality in immune function, including NK cell activity (45). Additionally, NK cell activity was decreased in depressed patients with alcoholism (12). A recent publication by Cook et al (13) showed a trend FIGURE 5.…”

Section: Discussionmentioning

confidence: 89%

“…Although some inconsistencies in findings exist, most studies indicate that NK cell cytotoxicity is reduced in ethanol-treated animals (5)(6)(7)(8)(9)(10). A few studies conducted using humans also show reduction in NK cell functions following alcohol administration (11)(12)(13). The mechanism by which ethanol alters NK cell function is not known.…”

Section: N Atural Killer Cells Have Been Implicated In Immune Surveilmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 89%

Section: N Atural Killer Cells Have Been Implicated In Immune Surveilmentioning

confidence: 99%

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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“…Depressed individuals show reduced NKCC, blunted mitogen-stimulated lymphocyte proliferative responses, and suppressed delayed-type hypersensitivity reactions (2)(3)(4)(5). There are, however, a number of questions that remain about immune differences between depressed and normal individuals.…”

Section: Introductionmentioning

confidence: 99%

“…Research examining the mediational role of health practices has also yielded negative findings. Specifically, the implementation of statistical controls for smoking, alcohol and caffeine consumption, weight change, and nutrition does not attenuate the association between depression and immune parameters (3,4,8,(11)(12)(13). Irwin et al (25,32) showed that sleep disturbances can modulate NKCC in both depressed and nondepressed individuals but did not evaluate…”

Section: Introductionmentioning

confidence: 99%

Pathways Linking Major Depression and Immunity in Ambulatory Female Patients

Miller

Cohen

Herbert

1999

Psychosomatic Medicine

124

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Objectives: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship. Methods: We studied 32 women who met Diagnostic and Statistical Manual of Mental Disorder, fourth edition, criteria for major depressive disorder and 32 healthy female control subjects. The groups were matched for age and ethnicity. None were taking medication, and all were free of disease involving the immune system. Results: Depressed subjects had reduced proliferative responses to the mitogens concanavalin A and phytohemagglutinin compared with control subjects. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation. Conclusions: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.

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“…NK cells quickly respond to immune activation signals, and activated NK cells circulate through blood and lymph and accumulate at the sites of injuries, infections, and tumors (1)(2)(3). A reduced NK cell cytolytic activity and increased incidence of certain forms of cancers and infections have been documented in chronic alcoholics (3)(4)(5)(6)(7)(8)(9)(10).…”

Section: Opioid Antagonist Naltrexone Disrupts Feedback Interaction Bmentioning

confidence: 99%

Opioid Antagonist Naltrexone Disrupts Feedback Interaction between μ and δ Opioid Receptors in Splenocytes to Prevent Alcohol Inhibition of NK Cell Function

Boyadjieva

Chaturvedi

Poplawski

et al. 2004

The Journal of Immunology

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Naltrexone, an opioid antagonist, has been used in clinical trials to treat alcoholism. As the opioid peptides β-endorphin and enkephalin increase splenic NK cell function in laboratory animals, it is anticipated that naltrexone treatment will cause immunosuppression. However, we report in this study that chronic naltrexone administration in laboratory rats increases the cytolytic activity of NK cells. It also prevents alcohol’s suppressive effect on these cells. We identified that, in the splenocytes, δ opioid receptor expression is tightly controlled by negative feedback regulation of μ opioid receptors. Naltrexone disrupts this feedback control by reducing μ opioid receptor function, thereby up-regulating δ opioid receptor binding, which results in an enhanced NK cell cytolytic response to δ opioid receptor ligands. We conclude that naltrexone, which has been shown to be a promising agent for the clinical management of alcoholism, may have potential use in the treatment of immune deficiency in alcoholic and nonalcoholic patients.

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Major Depressive Disorder, Alcoholism, and Reduced Natural Killer Cell Cytotoxicity

Cited by 159 publications

References 51 publications

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

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

Pathways Linking Major Depression and Immunity in Ambulatory Female Patients

Opioid Antagonist Naltrexone Disrupts Feedback Interaction between μ and δ Opioid Receptors in Splenocytes to Prevent Alcohol Inhibition of NK Cell Function

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