title: In vitro exposure to peptidic delta opioid receptor antagonists results in limited immunosuppression.
abstract: Previous studies by our group have demonstrated that in vitro exposure to delta-opioid receptor agonists results in a significant immunostimulation, whereas in vitro exposure to non-peptidic delta-opioid receptor antagonists results in significant suppression of various immune functions. The present study assessed potential immunomodulation by the peptidic delta-opioid receptor antagonists TIPP, D-TIPP, and ICI 174864 using a panel of in vitro immune function assays. Splenocytes from female B6C3F1 mice were cultured with the peptides at concentrations of 0.00001-10 microM. B cell proliferation was quantified following cellular activation, T cell function was assessed by cytokine production following stimulation with anti-CD3 monoclonal antibody, natural immunity was assessed by quantitating natural killer (NK) cell activity following a 24-h exposure, and macrophage function was assessed by quantification of interleukin-6 (IL-6) production. None of the peptides examined significantly affected B cell proliferation. Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-TIPP, but was significantly suppressed at 10 microM ICI 174864. Production of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI 174864. IL-6 production by macrophages was unaffected except for sporadic incidents of enhanced production in cells exposed to ICI 174864. NK cell function exhibited a differential pattern of suppression, with the greatest degree of suppression observed following exposure to TIPP and only slight suppression in cells exposed to either D-TIPP or ICI 174864. These data suggest that peptidic delta-opioid receptor antagonists do not exhibit the same pattern or degree of immunosuppressive activity as the non-peptidic antagonists at equivalent in vitro concentrations.
authors.affiliation: Life Sciences Department, IIT Research Institute, Chicago, IL 60616, USA. rhouse@iitri.com
authors.forename: R V
authors.initials: RV
authors.lastname: House
authors.forename: P T
authors.initials: PT
authors.lastname: Thomas
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D044005:Tetrahydroisoquinolines
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D044005:Tetrahydroisoquinolines; C082263:tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine; D004743:Enkephalin, Leucine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine