Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

BackgroundCumulating evidence has revealed the effectiveness of acupuncture therapy in relieving pain via immunoregulation. However, its underlying mechanism remains unknown. The present study was designed to determine the changes of immunogenic responses at different time-points of electroacupuncture (EA) interventions in neuropathic pain rats.MethodsThe neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EA was applied at Zusanli (ST36) and Yanglingquan (GB34) for the EA groups. The thermal pain threshold was detected with an algesia-detector. The subgroups of plasma and splenic lymphocytes were determined via fluorescence-activated cell sorting. Specific inflammatory cytokines were assayed using an ELISA-based bead multiplex assay. The activities of splenic natural killer (NK) cells and cytotoxic T lymphocytes were detected by methyl thiazolyl tetrazolium colorimetric method. For confirming the involvement of NK cell in EA-analgesia, anti-asialo-ganglio-N-tetraosylceramide (anti-asialo-GM1) antibody was given to CCI rats before EA.ResultsFollowing CCI, the thermal pain threshold of the affected hind footpad was significantly decreased, and increased from the 3rd day to the 12th day after EA interventions, presenting a time-dependent tendency from the 5th day on. From day 3 to 5 of EA interventions, the percentages and activity of splenic NK cells, concentrations of splenic interleukin-2 (IL-2) and beta-endorphin (β-EP) were significantly increased. Meanwhile, the concentrations of plasma IL-2, IL-1β and gamma-interferon (IFN-γ) were significantly decreased and returned to the normal level on day 12 following EA. Plasma transforming growth factor-β (TGF-β) levels were considerably upregulated on day 5 and 12 following EA. The CD4+/CD8+ T cell ratio was markedly downregulated compared with the control and CCI groups on day 5 and returned to the normal level on day 12 following EA. After depleting NK cells by anti-asialo-GM1 antibody, the increased thermal pain threshold following EA intervention was obviously reduced.ConclusionsRepeated EA interventions have a time-dependent cumulative analgesic effect in neuropathic pain rats, which is closely associated with its regulatory effects on NK cells, splenic IL-2, β-EP, and plasma IL-2, IL-1β, IFN-γ and TGF-β levels.

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“…β-EP has also been reported to increase NK cell activity [25]. Therefore, we investigated its concentration in plasma, spleen and hypothalamus.…”

Section: Resultsmentioning

confidence: 99%

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

Gao

Wang

et al. 2014

BMC Complement Altern Med

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“…In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the arcuate nucleus. The results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of pro-inflammatory cytokines in neuroendocrine and immune cells [130].…”

Section: Alcoholmentioning

confidence: 98%

“…To evaluate the effects of ethanol on the proinflammatory and anti-inflammatory cytokines known to control b-endorphin neuronal and NK cell functions during immune challenges the effects of chronic ethanol consumption on the basal and LPS-activated NK cells' functions in the spleen, the b-endorphin peptide precursor POMC gene expression in the arcuate nucleus of the hypothalamus, and mRNA levels of pro-inflammatory cytokines IL-1beta, TNF-a and anti-inflammatory cytokines IL-6 and IL-10 were measured in the spleen and in the ARC [130]. Ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen.…”

Section: Alcoholmentioning

confidence: 99%

Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction

Esquifino

Cano

Jiménez-Ortega

et al. 2007

Endocr

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Virtually all neuroendocrine and immunological variables investigated in animals and humans display biological periodicity. Circadian rhythmicity is revealed for every hormone in circulation as well as for circulating immune cells, lymphocyte metabolism and transformability, cytokines, receptors, and adhesion molecules. Clock genes, notably the three Period (Per1/Per2/Per3) genes and two Cryptochrome (Cry1/Cry2) genes, are present in immune and endocrine cells and are expressed in a circadian manner in human cells. This review discusses the circadian disruption of hormone release and immune-related mechanisms in several animal models in which circulating cytokines are modified including rat adjuvant arthritis, social isolation in rats and rabbits and alcoholism, the aging process and calorie restriction in rats. In every case the experimental manipulation used perturbed the temporal organization by affecting the shape and amplitude of a rhythm or by modifying the intrinsic oscillatory mechanism itself.

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“…Therefore neuroanatomical potential exists for a functional interaction between cytokines and corticotrophin-releasing hormone/arginine vasopressin in activating the HPA axis. There are quite distinct tissue-specific patterns of IL-1beta expression at different timepoints over 24 h following LPS injection [10] which may explain discrepant results in the literature of cytokine expression in subdivisions of the hypothalamus [28,31]. The pattern of expression, and protein content, of IL-1beta and other cytokines within the hypothalamus relative to changes in stress-responsive neuropeptides and neurotransmitters 21 days following LPS, in response to a second injection of LPS as described in our protective model [15,20], may provide insight into brain-immune interactions at a central level in mediating responses to stress.…”

mentioning

confidence: 91%

New Insights into Cytokine Gene Expression in the Rat Hypothalamus Following Endotoxin Challenge

2009

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Peripheral injection of the endotoxin LPS in rats 3 weeks prior to a second injection of LPS derived from another bacterial strain results in elevated corticosterone and decreased pro-inflammatory cytokines in the blood. We further investigated this model by measuring cytokine expression in the hypothalamus and spleen. In LPS-pretreated rats, hypothalamic expression of a range of cytokines was attenuated in response to the second injection of LPS while splenic expression was elevated. This is the first demonstration that prior exposure to an endotoxin can differentially affect cytokine expression in the brain and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. Changes in hypothalamic cytokine expression in endotoxin pretreated rats may provide new evidence for the involvement of central cytokine pathways in modulating peripheral inflammation and mediating psychopathological alterations associated with inflammatory diseases.

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Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

Cited by 22 publications

References 51 publications

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction

New Insights into Cytokine Gene Expression in the Rat Hypothalamus Following Endotoxin Challenge

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