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

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 . 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.