MORPHINE EFFECTS ON IMMUNE CELLS

Project: Research project

Description

A correlation between chronic morphine use and immunosuppression has been
well established in the recent past. However, the detailed mechanisms by
which morphine affects the immune system is not yet characterized. Recent
studies have shown that morphine treatment affects all the three major
components of the immune system; T-lymphocytes, B-lymphocytes and
macrophages. The effects ranged from changes in the weight of primary
lymphoid organs, alterations in the ratio of T-cell subpopulations and
responsiveness to cytokines. Since, T-lymphocytes play a central role in
immune response and modulate the function of other immunocompetent cells,
it is important to investigate the mechanism of morphine action on T-cells.
The activation of thymocytes/T-cells is regulated by the coordinate
production of cytokines and expression of cytokine receptors. The major
focus of this project is to determine the mechanisms by which morphine
inhibits IL-1 induced thymocyte and T-lymphocytes proliferation. This
proposal is based on the hypothesis that chronic morphine treatment blocks
the proliferative signaling pathways in thymocytes and T-lymphocytes by
either 1) inhibiting the expression of cytokine genes or 2) by down
regulating cytokine receptors or 30 by inhibiting signal transduction
pathway of cytokine receptors. Investigations will be carried out to
determine the direct and indirect mechanism by which morphine inhibits IL-2
synthesis in thymocytes and T-lymphocytes. Transcriptional regulation of
IL-2 synthesis and IL-2 receptor mediated signal transduction will be
investigated. These studies would help to understand the relationship
between morphine induced immunosuppression and the prevalence of HIV
infection in the drug abuse population. Since morphine is currently
administered chronically to patients suffering from cancer and other
intractable pain, the proposed investigation would be useful in preventing
generalized immunosuppression while retaining the analgesic properties of
opioids. It is therefore clinically important to study the mechanism of
morphine-induced immunosuppression.
StatusFinished
Effective start/end date1/1/946/30/99

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $82,761.00
  • National Institutes of Health: $90,582.00
  • National Institutes of Health

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Morphine
T-Lymphocytes
Thymocytes
Immunosuppression
Cytokine Receptors
Cytokines
Immune System
Signal Transduction
Interleukin-2 Receptors
Interleukin-1
Interleukin-2
Substance-Related Disorders
B-Lymphocytes
Intractable Pain
Gene Expression
Organ Size
Therapeutics
Opioid Analgesics
HIV Infections
Population