Effects of morphine and its metabolites on immune function in advanced cancer patients

Saori Hashiguchi, Hiroshi Morisaki, Yoshifumi Kotake, Junzo Takeda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Study Objective: To determine whether morphine and its active metabolites such as morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune function in patients with advanced cancer who required morphine for pain relief. Design: Prospective observational clinical study. Setting: Pain clinic of a university hospital. Patients: Fifteen patients who visited our clinic for control of advanced cancer pain. Interventions: During the initiation or changes of morphine therapy, venous blood samples were obtained at the enrollment of this study, 1 and 3 weeks after the change of morphine dose or route. Measurements: Lymphocyte subpopulation CD4+ and CD8 +, activity of natural killer cell, phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin M and G concentrations were measured, as well as plasma concentrations of morphine, M-3-G, and M-6-G. Main Results: At the entry of the study, 6 patients did not receive any type of morphine medication (group 1), whereas 9 patients were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the entry period, was reduced to 2 of 10 (visual analogue scale) during the study periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were significantly less than those in Group 2, plasma concentrations of immunologic markers were similar between the groups. In Group 1, Spearman linear regression analysis showed negative correlation between morphine-derived metabolites and immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was found with all immunologic parameters in Group 2. Stepwise linear regression analyses showed that the metabolites, rather than morphine per se, modulated immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin G concentration in Group 1. Conclusions: The present study suggests that some of humoral and cellular immunity are modulated by morphine-derived metabolites at the early phase of morphine therapy in patients with advanced cancer.

Original languageEnglish
Pages (from-to)575-580
Number of pages6
JournalJournal of Clinical Anesthesia
Volume17
Issue number8
DOIs
Publication statusPublished - 2005 Dec

Fingerprint

Morphine
Neoplasms
Phytohemagglutinins
Cell Proliferation
T-Lymphocytes
Linear Models
Immunoglobulin G
Regression Analysis
Pain Clinics
Lymphocyte Subsets
Humoral Immunity
Visual Analog Scale
Cellular Immunity
Natural Killer Cells
Observational Studies
Immunoglobulin M
Immunoglobulins
Biomarkers
Pain
Therapeutics

Keywords

  • Cancer pain
  • Immunity
  • Morphine
  • Morphine-3-glucuronide
  • Morphine-6-glucuronide

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Effects of morphine and its metabolites on immune function in advanced cancer patients. / Hashiguchi, Saori; Morisaki, Hiroshi; Kotake, Yoshifumi; Takeda, Junzo.

In: Journal of Clinical Anesthesia, Vol. 17, No. 8, 12.2005, p. 575-580.

Research output: Contribution to journalArticle

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abstract = "Study Objective: To determine whether morphine and its active metabolites such as morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune function in patients with advanced cancer who required morphine for pain relief. Design: Prospective observational clinical study. Setting: Pain clinic of a university hospital. Patients: Fifteen patients who visited our clinic for control of advanced cancer pain. Interventions: During the initiation or changes of morphine therapy, venous blood samples were obtained at the enrollment of this study, 1 and 3 weeks after the change of morphine dose or route. Measurements: Lymphocyte subpopulation CD4+ and CD8 +, activity of natural killer cell, phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin M and G concentrations were measured, as well as plasma concentrations of morphine, M-3-G, and M-6-G. Main Results: At the entry of the study, 6 patients did not receive any type of morphine medication (group 1), whereas 9 patients were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the entry period, was reduced to 2 of 10 (visual analogue scale) during the study periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were significantly less than those in Group 2, plasma concentrations of immunologic markers were similar between the groups. In Group 1, Spearman linear regression analysis showed negative correlation between morphine-derived metabolites and immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was found with all immunologic parameters in Group 2. Stepwise linear regression analyses showed that the metabolites, rather than morphine per se, modulated immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin G concentration in Group 1. Conclusions: The present study suggests that some of humoral and cellular immunity are modulated by morphine-derived metabolites at the early phase of morphine therapy in patients with advanced cancer.",
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