Secretion of inflammatory mediators by isolated rat Kupffer cells: the effect of octreotide.
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.
Valatas
Vassilis
V
Gastroenterology Department, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, GR-71409, Greece.
Kolios
George
G
Manousou
Pinelopi
P
Xidakis
Costas
C
Notas
George
G
Ljumovic
Dusanka
D
Kouroumalis
Elias A
EA
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
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