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


METHODS
Prospective observational clinical study.


METHODS
Pain clinic of a university hospital.


METHODS
Fifteen patients who visited our clinic for control of advanced cancer pain.


METHODS
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.


METHODS
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.


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.
Hashiguchi
Saori
S
Department of Anesthesiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Morisaki
Hiroshi
H
Kotake
Yoshifumi
Y
Takeda
Junzo
J
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000097:blood / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007075:Immunoglobulin M / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood / Q000494:pharmacology*; D009369:Neoplasms / Q000276:immunology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000187:drug effects
D000701:Analgesics, Opioid; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009020:Morphine