title: Opioids modulate constitutive B-lymphocyte secretion.
abstract: The opioid system plays a major role in immunomodulation, while its action on cells of the immune system may be opioid receptor-mediated or not. Opioid effects on B-lymphocytes are considered as indirect, attributed to an interplay between distinct cell populations. The aim of the present study was to investigate whether opioid agonists (morphine, alpha(S1)-casomorphin and ethylketocyclazocine) may have a direct action on the secretion of antibodies and cytokines by multiple myeloma-derived cell lines and normal CD19+ B-lymphocytes. Our results show that opioids modulate antibody and cytokine secretion by multiple myeloma cells in a cell line-dependent and opioid receptor-independent manner, while they decrease antibody secretion by normal B-lymphocytes. Furthermore, they decrease the proliferation rate of multiple myeloma cells through opioid receptor activation. Our data suggest two different mechanisms of action of opioids, mediated by different signaling pathways: an early non-opioid receptor-related effect, modulating the constitutive immunoglobulin and cytokine secretion, and a long-term receptor-mediated action on cell growth. These data suggest a further opioid implication in the control of humoral immunity.
authors.affiliation: Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Vassou
authors.forename: Efstathia
authors.initials: E
authors.lastname: Bakogeorgou
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Helen
authors.initials: H
authors.lastname: Dimitriou
authors.forename: Anastassia
authors.initials: A
authors.lastname: Hatzoglou
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002364:Caseins / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016314:Ethylketocyclazocine / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D007378:Interleukins / Q000096:biosynthesis; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D018941:Antigens, CD19; D002364:Caseins; D016207:Cytokines; D007136:Immunoglobulins; D007378:Interleukins; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C102368:alpha(S1)-casomorphin; D016314:Ethylketocyclazocine; D048051:p38 Mitogen-Activated Protein Kinases