Effect of morphine sulfate on neonatal neutrophil chemotaxis

Clin J Pain. 2008 Jan;24(1):76-82. doi: 10.1097/AJP.0b013e3181582c76.


Background: Opioids have been increasingly used for pain control in the neonatal intensive care unit. Data from adult human studies have demonstrated suppressive effects of morphine sulfate on the immune system, owing in part to its inhibition of chemotaxis.

Objective: To study the effect of morphine exposure on chemotaxis of newborn neutrophils compared with adult neutrophils.

Methods: Blood samples were collected from adult controls and from the umbilical cord of healthy full-term newborns. Neutrophils were isolated and then exposed to morphine sulfate. Chemotaxis assays were performed using interleukin (IL)-8 as the chemoattractant. The migrated neutrophils were quantitated by flow cytometry. IL-8 receptor expression was evaluated by staining with an anti-IL-8 receptor-specific antibody. Chemotaxis and IL-8 receptor expression were compared between newborn and adult neutrophils.

Results: There was no difference in random migration between adult (n=10) and newborn neutrophils (n=14). IL-8 efficiently induced chemotaxis of both adult and newborn neutrophils, although newborn neutrophils exhibited significantly decreased chemotaxis compared with adult neutrophils: 389+/-197 newborn cells versus 731+/-190 adult cells (P=0.025). Exposure to morphine sulfate did not decrease chemotaxis of adult neutrophils but did modestly impair chemotaxis of newborn neutrophils. After exposure to morphine sulfate, adult neutrophils showed no difference in IL-8 receptor expression, whereas newborn neutrophils expressed fewer IL-8 receptors.

Conclusions: Newborn neutrophils had reduced chemotaxis toward IL-8. Exposure to morphine sulfate further decreased their chemotactic function. The differential effect may be explained in part by the reduction of IL-8 receptors of newborn neutrophils after morphine exposure.

MeSH terms

  • Adult
  • Analgesics, Opioid / pharmacology*
  • Cell Separation
  • Cell Survival / drug effects
  • Chemotaxis, Leukocyte / drug effects*
  • Humans
  • In Vitro Techniques
  • Infant, Newborn / blood*
  • Interleukin-8 / metabolism
  • Leukocyte Count
  • Morphine / pharmacology*
  • Neutrophils / drug effects*
  • Receptors, Interleukin-8 / drug effects
  • Receptors, Interleukin-8A / drug effects
  • Spectrometry, Fluorescence


  • Analgesics, Opioid
  • Interleukin-8
  • Receptors, Interleukin-8
  • Receptors, Interleukin-8A
  • Morphine