title: Increased tumor necrosis factor-alpha and nitric oxide production by rat macrophages following in vitro stimulation and intravenous administration of the delta-opioid agonist SNC 80.
abstract: Opioids alter immune function by binding to opioid receptors on cells of the immune system, or indirectly by acting on receptors within the central nervous system. Mu-selective opioid agonists are generally associated with immunosuppression, whereas delta-opioid receptor-selective agonists are commonly associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the nonpeptide delta-opioid receptor agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC 80) did not alter certain parameters of immunocompetence. In the present study, we studied the in vitro and ex vivo effects of SNC 80 on rat macrophage and lymphocyte functions. We showed that SNC 80 at concentrations of 10(-7) M and 10(-6) M, significantly (P < 0.01) stimulated the in vitro production of tumor necrosis factor-alpha (TNF-alpha) (60-100% increase) and nitric oxide (34-67% increase) by resident and LPS-stimulated peritoneal macrophages. Similarly, intravenous administration of SNC 80 (6.8 mg/kg) significantly (P < 0.01) increased the production of TNF-alpha and nitric oxide (2- and 1.5-fold increases respectively, compared with saline-injected control) by LPS-stimulated splenic macrophages. In addition, intravenous injection of SNC 80 plus Con A potentiated ex vivo LPS-stimulated macrophage functions. SNC 80 could potentially be utilized in various clinical situations where immunosuppression is undesirable.
authors.affiliation: Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria 61656, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gomez-Flores
authors.forename: K C
authors.initials: KC
authors.lastname: Rice
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: R J
authors.initials: RJ
authors.lastname: Weber
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017465:Receptors, Opioid, delta / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000276:Adjuvants, Immunologic; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; D014409:Tumor Necrosis Factor-alpha; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009569:Nitric Oxide