Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity in volunteers

Anesthesiology. 1995 Sep;83(3):500-8. doi: 10.1097/00000542-199509000-00008.


Background: Opioids are used by patients who have conditions ranging from the acute pain of surgery and chronic cancer pain to substance abuse. Despite their widespread use and considerable experimental data about them, little is known about how opioids may alter in vivo immunity in humans. This study was designed to evaluate the in vivo effect of morphine on human peripheral blood immune functions.

Methods: Healthy volunteers underwent continuous exposure to morphine for 36 h including a 24-h intravenous infusion in the hospital. Peripheral blood was drawn for immune function studies at five measurement times before, during, and after morphine exposure. Peripheral blood mononuclear cells were tested for acute and gamma-interferon-stimulated natural killer cell cytotoxicity (NKCC), antibody-dependent cell cytotoxicity, antibody Fc receptor expression, and human immunodeficiency virus infectivity.

Results: Significant suppression of NKCC was observed at 2 and 24 h after the onset of intravenous morphine exposure. Suppression of NKCC persisted for 24 h after termination of morphine infusion in a "high"-dose study group. gamma-Interferon-stimulated NKCC and antibody-dependent cell cytotoxicity were also decreased after 24 h of intravenous morphine exposure. No effect on Fc receptor expression was observed. Mean virus antigen production after lymphocyte infection with human immunodeficiency virus was not increased (p24 100 ng/ml after morphine vs. 43 ng/ml before morphine; P = 0.17).

Conclusions: These results suggest that morphine administration, at doses within the range of analgesic use, can cause measurable suppression of some components of the human cellular immune system.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cytotoxicity, Immunologic / drug effects*
  • Female
  • HIV Core Protein p24 / analysis
  • Humans
  • Interferon-gamma / pharmacology*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Morphine / pharmacology*
  • Receptors, Fc / analysis


  • HIV Core Protein p24
  • Receptors, Fc
  • Morphine
  • Interferon-gamma