Secretion of inflammatory mediators by isolated rat Kupffer cells: the effect of octreotide

Aims: 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 TNTalpha, 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 TNFa (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 approximate to 0.05) production by LPS-activated KC. These effects were reversed with Wortmannin pretreatment 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. (C) 2004 Elsevier B.V. All rights reserved.