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J Interferon Cytokine Res. 1999 Jun;19(6):625-30.

Inhibition of interleukin-2 production and downregulation of IL-2 and transferrin receptors on rat splenic lymphocytes following PAG morphine administration: a role in natural killer and T cell suppression.

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  • 1Department of Biomedical and Therapeutic Sciences, University of Illinois, College of Medicine, Peoria 61656, USA.


We investigated the effects of acute injection of morphine into the rat mesencephalon periaqueductal gray (PAG), on splenic natural killer (NK) cell and lymphocyte functions, interleukin-2 (IL-2) production, expression of T cell (CD3), T helper cell (CD4), T suppressor cell (CD8), and NK cell (NKR-P1) surface markers, and expression of IL-2 (CD25) and transferrin (CD71) receptors. Bilateral microinjection of 10 nmol of morphine in the PAG significantly (p < 0.001) inhibited IL-2 (31%) production by activated splenic lymphocytes compared with that of PAG saline-injected control rats. In addition, morphine significantly (p < 0.01) suppressed splenic NK cell activity (14-33%) and T lymphocyte proliferative responses (25-48%) to various mitogens compared with controls. Furthermore, morphine did not alter the expression of CD3, CD4, CD8, and NKR-P1 surface markers, but significantly (p < 0.001) downregulated the expression of CD25 and CD71 receptors following in vitro activation. These results suggested that injection of morphine in the PAG suppresses NK and T cell functions by reducing the ability of T cells to produce IL-2 and downregulating the expression of CD25 and CD71 surface activation markers.

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