Immunosuppression by morphine-induced lymphocyte apoptosis: Is it a real issue?

Takeshi Ohara, Tsunetoshi Itoh, Masahiko Takahashi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Morphine has been an optimal choice for cancer pain management. However, several recent studies suggested that morphine induces apoptosis in human peripheral blood lymphocytes (PBLs), raising a serious concern about the use of opioid-based analgesic strategies. In this study, therefore, we aimed to evaluate whether morphine induced apoptosis in cultured human PBLs. Apoptotic events were assessed by flow-cytometrical detection of surface phosphatidylserine and nuclear fragmentation, as well as Fas, Bcl-2, and Caspase-3 activity in PBLs gated on a light-scatter basis. Peripheral blood mononuclear cells isolated from healthy subjects were cultured with etoposide, morphine, or vehicle (medium) for 48 h. During co-culture with etoposide, apoptosis was significantly induced in PBLs, and the cells did not survive for 48 h. In comparison, morphine had no effect on the expression rate of any of the detected molecules, suggesting that no apparent apoptotic processes were induced during the incubation. Furthermore, co-incubation with a Fas-specific antibody did not increase apoptotic cell rates in the morphine cultures. These results do not support the hypothesis that morphine directly modulates PBL apoptosis resulting in immunosuppression. We believe that the choice of opioids for optimal pain relief should not be discouraged until further studies clarify this issue.

Original languageEnglish
Pages (from-to)1117-1122
Number of pages6
JournalAnesthesia and Analgesia
Issue number4
Publication statusPublished - 2005 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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