Effect of N-methyl-D-aspartate receptor antagonist on T helper cell differentiation induced by phorbol-myristate-acetate and ionomycin

Gao, Mengchun; Jin, Wenjie; Qian, Yanning; Ji, Lulu; Feng, Genbao; Sun, Jie

doi:10.1016/j.cyto.2011.06.022

Cited by 29 publications

(23 citation statements)

References 31 publications

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“…However, in the present study, ketamine shifted the balance of Th1/Th2 toward Th1, suggesting that it may have a beneficial immunoregulatory effect in patients with CRC. This supports the findings of a previous study in healthy participants, in which ketamine suppressed the differentiation of Th cells and secretion of cytokines, whereas the Th1/Th2 ratio was increased in the presence of PMA and ionomycin (16).…”

Section: Discussionsupporting

confidence: 92%

“…It has previously been demonstrated that anesthetic and sedative agents exhibit immunomodulatory activity (15). For example, the effects of morphine and ketamine on the differentiation of Th cells have been demonstrated in previous studies in healthy volunteers in vitro (16,17). To the best of our knowledge, no previous studies have investigated whether morphine and ketamine are able to alter the differentiation of Th cells in patients with tumors; therefore, this study was designed to assess the effects of morphine and ketamine on the differentiation of CD4 + T cells induced by phorbol-myristate-acetate (PMA) and ionomycin in patients with CRC.…”

Section: Morphine and Ketamine Treatment Suppress The Differentiationmentioning

confidence: 95%

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Morphine and ketamine treatment suppress the differentiation of T helper cells of patients with colorectal cancer in�vitro

Hou

Zhou

et al. 2018

Exp Ther Med

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There have been conflicting reports regarding the effects of anesthetic and analgesic drugs on immune function in patients with cancer. The aim of the present study was to investigate changes to T helper (Th) cell populations in patients with colorectal cancer (CRC) and to assess the effects of morphine and ketamine on the differentiation of Th cells harvested from patients with CRC in vitro. Peripheral blood samples were extracted from 20 patients with CRC and 20 healthy participants. Peripheral blood mononuclear cells were isolated and incubated in a solution containing phorbol-myristate-acetate (PMA) and ionomycin in the presence or absence of morphine or various ketamine concentrations (25, 50, and 100 µM). Samples were analyzed 4 h later. Th1 and Th2 cells were significantly increased by PMA and ionomycin stimulation; however, Th1 cells and the Th1/Th2 ratio in PMA and ionomycin treatments were significantly decreased in the CRC group compared with the control group. Following incubation with PMA and ionomycin, morphine significantly decreased Th1 cells and the Th1/Th2 ratio in the CRC group. Ketamine did not significantly affect levels of Th1 or Th2 cells or the Th1/Th2 ratio at a concentration of 25 µM; however, a significant increase in the Th1/Th2 ratio was observed at a concentration of 50 µM and, at 100 µM, a significant decrease in Th1 and Th2 cells and an increase in the Th1/Th2 ratio were observed. The present study suggests that CRC may shift the balance of Th1/Th2 towards Th2 by inducing an immunological response, morphine is able to suppress the differentiation of Th cells and decreases the Th1/Th2 ratio, and ketamine may affect the differentiation of Th cells in a dose-dependent manner.

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Section: Discussionsupporting

confidence: 92%

Section: Morphine and Ketamine Treatment Suppress The Differentiationmentioning

confidence: 95%

Morphine and ketamine treatment suppress the differentiation of T helper cells of patients with colorectal cancer in�vitro

Hou

Zhou

et al. 2018

Exp Ther Med

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“…Does ketamine interferes with this important immune ratio? Experimental in vitro data using CD4‐positive lymphocytes separated from healthy volunteers clearly show that ketamine used at concentration of 10 μg/mL (a concentration comparable with the one obtained after an IV bolus of 0.5 mg/kg) significantly increased the Th1/Th2 ratio and might consequently be benefit to the patient's global immune function . In comparison with morphine (used in the same model at human analgesic concentration), both drugs reduce the rate of Th cell differentiation and subsequent cytokines production simulation.…”

Section: Ketamine As a “Regulator” Of The Inflammatory Reaction: Precmentioning

confidence: 92%

Ketamine and Peripheral Inflammation

2013

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The old anesthetic ketamine has demonstrated interactions with the inflammatory response. This review intends to qualify the nature and the mechanism underlying this interaction. For this purpose, preclinical data will be presented starting with the initial works, and then, the probable mechanisms will be discussed. A summary of the most relevant clinical data will be presented. In conclusion, ketamine appears as a unique "homeostatic regulator" of the acute inflammatory reaction and the stress-induced immune disturbances. This is of some interest at a moment when the short- and long-term deleterious consequences of inadequate inflammatory reactions are increasingly reported. Large-scale studies showing improved patient's outcome are, however, required before to definitively assert the clinical reality of this positive effect.

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“…Our previous studies found that ketamine, a potent anesthetic and analgesic drug [11,12], can increase Th1/ Th2 ratio and thus might be benefit to the immunological function [13]. But ketamine is not the common analgesics for acute postoperative pain or chronic pain.…”

Section: Introductionmentioning

confidence: 99%

Morphine, but Not Ketamine, Decreases the Ratio of Th1/Th2 in CD4-positive Cells Through T-bet and GATA3

Gao¹,

Sun²,

Jin³

et al. 2011

Inflammation

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This study was conducted to investigate the effect of morphine on CD4-positive T cells differentiation and the transcriptional factors induced by phorbol myristate acetate (PMA) and ionomycin. CD4-positive lymphocytes separated from healthy volunteers were incubated by PMA (25 ng/ml) + ionomycin (1 μg/ml) with or without the presence of morphine, ketamine, or naloxone. Th subsets, supernatant cytokines, and transcriptional factors were detected 4 h later. Th1 and Th2 cells, levels of INF-γ, IL-2, IL-4 and the activities of T-bet and GATA3 were significantly increased after incubation with PMA and ionomycin. However, the number of Th1 cells, Th1/ Th2, the levels of INF-γ and INF-γ/IL-4, and the activities and protein levels of T-bet and GATA3 were decreased after incubation with PMA and ionomycin in the presence of morphine. Naloxone can abolish morphine's suppressive effect on Th cell differentiation. Morphine has a negative effect on Th cell balance induced by PMA and ionomycin, the mechanism is related to T-bet and GATA3.

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Effect of N-methyl-D-aspartate receptor antagonist on T helper cell differentiation induced by phorbol-myristate-acetate and ionomycin

Cited by 29 publications

References 31 publications

Morphine and ketamine treatment suppress the differentiation of T helper cells of patients with colorectal cancer in�vitro

Morphine and ketamine treatment suppress the differentiation of T helper cells of patients with colorectal cancer in�vitro

Ketamine and Peripheral Inflammation

Morphine, but Not Ketamine, Decreases the Ratio of Th1/Th2 in CD4-positive Cells Through T-bet and GATA3

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