Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules

J Neuroimmunol. 2003 Nov;144(1-2):16-27. doi: 10.1016/s0165-5728(03)00273-x.

Abstract

We have previously shown that abstinence from morphine by either abrupt (AW) or precipitated (PW) withdrawal induces greater than 80% suppression in the capacity to mount an in vitro plaque-forming cell (PFC) response to sheep red blood cells at 24-h post withdrawal. Present studies on the mechanisms of immunosuppression showed that addition of normal unfractionated spleen cells, macrophage-enriched adherent cells, or CD11b(+) purified macrophages, to spleen cells taken from withdrawn mice, restored immune responses. Spleen cells from mice undergoing withdrawal also had decreased splenic mRNA and/or protein levels of IL-1beta, IL-1Ra, TNF-alpha, IL-12, and IFN-gamma. Addition of IL-1beta or IFN-gamma to AW cultures was able to reverse their immunosuppression. These results strongly suggest that morphine withdrawal results in a deficit of macrophage function.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • Antigens, CD / biosynthesis
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B7-1 Antigen* / metabolism
  • B7-2 Antigen
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • Hemolytic Plaque Technique
  • Immunosuppressive Agents / adverse effects*
  • Leukocyte Count
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C3H
  • Morphine / adverse effects*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology*
  • Spleen / metabolism
  • Substance Withdrawal Syndrome / immunology*
  • Substance Withdrawal Syndrome / metabolism
  • Time Factors

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Cytokines
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • RNA, Messenger
  • Morphine