Depletion and recovery of lymphoid subsets following morphine administration

Br J Pharmacol. 2011 Dec;164(7):1829-44. doi: 10.1111/j.1476-5381.2011.01475.x.


Background and purpose: Opioid use and abuse has been linked to significant immunosuppression, which has been attributed, in part, to drug-induced depletion of lymphocytes. We sought to define the mechanisms by which lymphocyte populations are depleted and recover following morphine treatment in mice.

Experimental approach: Mice were implanted with morphine pellets and B- and T-cell subsets in the bone marrow, thymus, spleen and lymph nodes were analysed at various time points. We also examined the effects of morphine on T-cell development using an ex vivo assay.

Key results: The lymphocyte populations most susceptible to morphine-induced depletion were the precursor cells undergoing selection. As the lymphocytes recovered, more lymphocyte precursors proliferated than in control mice. In addition, peripheral T-cells displayed evidence that they had undergone homeostatic proliferation during the recovery phase of the experiments.

Conclusions and implications: The recovery of lymphocytes following morphine-induced depletion occurred in the presence of morphine and via increased proliferation of lymphoid precursors and homeostatic proliferation of T-cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Corticosterone / blood
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology*
  • Narcotics / pharmacology*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology


  • Analgesics, Opioid
  • Narcotics
  • Morphine
  • Corticosterone