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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Abstract
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.