Interaction between endogenous opioids and IL-2 on PHA-stimulated human lymphocytes.
Endogenous opioids exert a variety of extra central nervous system (CNS) functions, including modulation of some human lymphocyte functions. The latter opioid activity may result in elevation of human natural killer (NK) function (i.e. by beta-endorphin), which is reversed by an opioid antagonist, Naloxone. Since recent evidence has suggested both structural and functional similarities between lymphokines known to elevate human NK function (interferon and interleukin-2) and endogenous opioids, we investigated if Naloxone could modulate lymphokine-enhanced human NK activity. Naloxone blunted, in a dose-dependent fashion, the NK-enhancing activity of peripheral blood lymphocytes or large granular lymphocytes by recombinant interferon-alpha (IFN-alpha) or interleukin-2 (IL-2). Naloxone decreased the uptake of radiolabelled IL-2 receptors. beta-endorphin also decreased the binding of radiolabelled IL-2 or IL-2 receptor-positive human lymphocytes. Finally, labelled Naloxone was inhibited from binding to phytohaemagglutinin (PHA)-stimulated lymphocytes by either beta-endorphin or IL-2. These findings strongly suggest that human lymphocyte receptors for opioid, IFN or IL-2 molecules, once occupied, have distinct influences on the alternate receptor. In addition, these data further strengthen the potential role of CNS-mediated influences on the human immune system.
Department of Medicine, Minneapolis Veterans Administration Medical Center, MN 55417.
N E
NE
Kay
J E
JE
Morley
J I
JI
Allen
D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004723:Endorphins / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D009270:Naloxone / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D011994:Recombinant Proteins / Q000276:immunology
D004723:Endorphins; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D009270:Naloxone