Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
OPIOID PEPTIDE REGULATION OF HUMAN NATURAL KILLER ACTIVITY
Diss Abstr Int [B]; 50(1):116 1989. Unique Identifier : AIDSLINE ICDB/90658138 Oleson DR; Univ. of Nebraska Medical Center
Abstract:
The endogenous opioids are a ubiquitous class of neuropeptides which circulate in human plasma and show widespread distribution in the central and peripheral nervous system. The production and secretion of opioid peptides is not restricted to neurons; it also occurs in cells of lymphoreticular origin. However, the immunomodulatory role of the endogenous opioids remains largely uncharacterized. Therefore, the intent of this thesis is to delineate the effects of opioid peptides on an innate immune function, natural killer (NK) activity, and to explore the clinical potential of this interaction. Peripheral blood lymphocytes (PBL) were obtained from normal human donors and patients (pts) recruited from the Univ of Nebraska Viral Syndrome Clinic. PBL were stimulated with test peptides in vitro, incubated for 18 hr, and tested for NK activity. The cytotoxic potential of normal donors with low NK activity was enhanced by opioid peptides, while the NK activity of high responders was suppressed. The dose-response curve was bimodal with peak suppression occurring at 10(-12) M and peak enhancement occurring from 10(-10) M to 10(-8) M. High and low affinity binding sites, of at least one type of opioid receptor, were confirmed through use of selective opioid receptor agonists and purified populations of cells. NK activity was directly affected by opioid peptides at the first stage of cytolysis or target cell binding. The cytosolic free calcium levels of T-cell populations which had been expanded in culture with recombinant interleukin-2 was increased following opioid stimulation, suggesting an additional mechanism by which opioid peptides modify cell-mediated cytotoxicity. Opioid modulation of NK function was dependent on the activation stage of the effector population. The NK activity of pts infected with human immunodeficiency virus (HIV) was below normal and was consistently increased following opioid stimulation. These results confirmed the experiments performed with normal donors, and imply that opioid peptides may be useful therapeutically in the treatment of immunodeficient or immunocompromised pts. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD89-06851)
Keywords: *Cytotoxicity, Immunologic Endorphins/*PHYSIOLOGY Human HIV Infections/*IMMUNOLOGY Killer Cells, Natural/*IMMUNOLOGY Receptors, Opioid/PHYSIOLOGY THESIS 900228
M9020580
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Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
