title: Morphine and ketamine inhibit immune function of gastric cancer patients by increasing percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in vitro.
abstract: There is conflicting evidence regarding effects of anesthetic and analgesic drugs on immune function of cancer patients. This study was designed to observe changes of T cell subpopulations in the gastric cancer (GC) patients and to assess effects of morphine and ketamine on the CD4(+) T cells, CD8(+) T cells, and regulatory T cells (Tregs) populations obtained from the GC patients in vitro.
  
  
  
  The peripheral blood samples from 20 GC patients and 20 healthy volunteers were obtained. The peripheral blood mononuclear cells were isolated and incubated in a solution containing phorbol-myristate-acetate and ionomycin (2 μL/mL) in the presence or absence of morphine (50 ng/mL) or different-concentration ketamine (25, 50, and 100 μM). The CD4(+) T cells, CD8(+) T cells, and Tregs were determined using the flow cytometric assay.
  
  
  
  The percentages of CD8(+) T cells were significantly decreased, but the ratio of CD4(+)/CD8(+) T cells and Tregs populations was significantly increased in the GC control group compared with the normal control group (P < 0.05). The ratio of CD4(+)/CD8(+) T cells was significantly increased in the groups M and K3 compared with the control group (P < 0.05) but was significantly decreased in the group K1 compared with the group K3. The percentage of Tregs was significantly increased in the groups M, K1, K2, and K3 compared with the control group. With the increased concentrations, ketamine increased the number of Tregs.
  
  
  
  GC shifts the balance of CD4(+)/CD8(+) T cells toward CD4(+) T cells and increases the Tregs populations by inducing immune responses. Morphine increases the ratio of CD4(+)/CD8(+) T cells and Tregs populations. Ketamine affects the ratio of CD4(+)/CD8(+) T cells and Tregs populations in a dose-dependent model.
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China; Medicine and Life Sciences College of Shandong Academy of Medical Sciences, Jinan University, Jinan, Shandong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Nai-Bao
authors.initials: NB
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Xiu-Qin
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Xing-Wu
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: wangkg666@163.com.
authors.forename: Kai-Guo
authors.initials: KG
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: xuefushan@aliyun.com.
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Xue
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000778:Anesthetics, Dissociative / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007649:Ketamine / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000778:Anesthetics, Dissociative; D015415:Biomarkers; D007649:Ketamine; D009020:Morphine
keywords: CD4(+)/CD8(+) ratio; Gastric cancer; Ketamine; Morphine; Regulatory T cells