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Updated: Jan 28, 2026

Analysis of Human Natural Killer Cell Metabolism
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Analysis of Human Natural Killer Cell Metabolism

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Suppression of Human Natural Killer Cells by Different Classes of Opioids

Dermot P Maher1, Deepa Walia, Nicola M Heller

  • 1From the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland.

Anesthesia and Analgesia
|February 26, 2019
PubMed
Abstract

Insights

Certain opioids suppress natural killer cell activity, potentially explaining reduced cancer recurrence with opioid-sparing anesthesia. This effect is mediated by mu- and kappa-receptor agonism, not delta-receptors.

Area of Science:

  • Immunology
  • Pharmacology
  • Anesthesiology

Background:

  • Opioid-sparing anesthesia is linked to decreased cancer recurrence.
  • Opioids may suppress natural killer (NK) cell activity, a potential mechanism.
  • Systematic characterization of opioid class effects on NK cell cytotoxicity is lacking.

Purpose of the Study:

  • To investigate the impact of various opioid classes on human natural killer cell cytotoxicity.
  • To determine the receptor subtypes involved in opioid-mediated NK cell suppression.

Main Methods:

  • Human NK cells were isolated and incubated with clinically relevant opioids and receptor-specific agonists.
  • NK cell cytotoxicity was assessed by measuring tumor cell apoptosis after co-incubation.
  • The role of opioid receptor antagonists, including naloxone, was evaluated.

Main Results:

  • Morphine, methadone, buprenorphine, loperamide, and specific agonists ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin, U-50488) significantly reduced NK cell cytotoxicity.
  • Fentanyl, O-desmethyltramadol, and [D-Pen2,D-Pen5] enkephalin did not affect NK cell cytotoxicity.
  • Naloxone pretreatment blocked opioid-induced suppression, indicating receptor-mediated effects.

Conclusions:

  • Certain opioids, particularly mu- and kappa-receptor agonists, suppress human NK cell cytotoxicity.
  • This suppression is reversible with naloxone, confirming receptor involvement.
  • Findings suggest a mechanism linking opioid use, NK cell function, and cancer recurrence.

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