title: Secretion of inflammatory mediators by isolated rat Kupffer cells: the effect of octreotide.
abstract: OBJECTIVE
  We studied the production of inflammatory mediators by rat KC and the possible in vitro effect of the somatostatin analogue octreotide.
  
  
  METHODS
  Primary KC cultures were incubated with LPS added alone or with different concentrations of octreotide. The production of TNFalpha, IL-6, IL-10, IL-12 and IL-13 was assessed in culture supernatants by ELISA and that of nitric oxide (NO) by a modification of the Griess reaction.
  
  
  RESULTS
  Isolated KC produced a basal amount of TNFalpha, IL-6, IL-12, IL-13, and NO but not IL-10. LPS-stimulated KC secreted significantly increased amounts of TNFalpha (P < 0.001), IL-6 (P < 0.01), IL-10 (P < 0.001), IL-12 (P < 0.01), and NO (P < 0.001) whereas IL-13 production remained constant. Octreotide reduced IL-12 (P < 0.05) and increased IL-13 (P < 0.05) production by unstimulated KC. Furthermore, octreotide suppressed TNFalpha production (P < 0.05), without modifying TNFalpha mRNA expression and decreased iNOS expression and NO (P approximately 0.05) production by LPS-activated KC. These effects were reversed with Wortmannin pre-treatment suggesting that octreotide may act via interference with phosphatidylinositol 3-kinase pathways.
  
  
  CONCLUSIONS
  These data demonstrate that KC is a source of multiple inflammatory mediators, indicating a critical role in liver inflammatory disorders. Octreotide modulates inflammatory mediator production by isolated KC, suggesting that it might have immunoregulatory and anti-inflammatory effects in liver diseases.
authors.affiliation: Gastroenterology Department, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, GR-71409, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Valatas
authors.forename: George
authors.initials: G
authors.lastname: Kolios
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Manousou
authors.forename: Costas
authors.initials: C
authors.lastname: Xidakis
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Dusanka
authors.initials: D
authors.lastname: Ljumovic
authors.forename: Elias A
authors.initials: EA
authors.lastname: Kouroumalis
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018793:Interleukin-13; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D015282:Octreotide