High interleukin-6 production within the peritoneal cavity in decompensated cirrhosis and malignancy-related ascites.

To assess the diagnostic and prognostic value of interleukin-6, interleukin 1 beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured these cytokines in eight patients with malignancy-related ascites and 32 patients with decompensated cirrhosis. Five patients had an episode of bacterial peritonitis, during which one or more ascitic fluid samples were analyzed. Interleukin-6 and tumor necrosis factor-alpha were not significantly different between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/- 15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/- 604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml, plasma tumor necrosis factor-alpha 3.

Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis.

The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups.

Interactions between cytokines and eicosanoids: a study using human peritoneal macrophages.

To examine the interactions between the main pro-inflammatory cytokines and eicosanoids produced by human inflammatory cells, human peritoneal macrophages (hp-M phi) were isolated from ascitic fluid of patients with portal hypertension. Interactions between interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were studied by addition or inhibition of several cytokines and eicosanoids: human recombinant IL-1 beta (hrIL-1 beta) addition, LTB4 addition and 5-lipoxygenase inhibition (6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiaz ole hydrochloride (E6080)), PGE2 addition and cyclooxygenase inhibition (indomethacin). In hp-M phi hrIL-1 beta stimulated the LTB4 production, while the PGE2 production was inhibited.

Changes in Eicosanoid and Tumour Necrosis Factor-alpha Production by Rat Peritoneal Macrophages During Carrageenin-Induced Peritonitis.

Changes and correlations in cytokine and eicosanoid production by blood monocytes, non-purified and purified peritoneal cells during a carrageenin-induced peritonitis were investigated for a period of ten days. The cells were isolated and stimulated in vitro. Cytokine and eicosanoid production of the non-purified fraction increased steadily during peritonitis.

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFalpha.

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid.

Inflammatory mediators and activity of human peritoneal macrophages.

Human peritoneal macrophages (hp-M phi) are a source of inflammatory mediators. After stimulation in vitro for 24 h with LPS there was a significant increase in cytokine production (IL-1, IL-6 and TNF alpha), but not in the production of eicosanoids from endogenous arachidonate. Leukotrienes are the predominant eicosanoids formed after stimulation with calcium ionophore for 15 min, while prostaglandin formation is insignificant.

Eicosanoid production by density-defined human peritoneal macrophages during inflammation.

Density-defined macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 (LTB4, 16%) and 5-hydroxy-eicosatetraenoic acid (5-HETE, 24%) and the cyclooxygenase products 12-hydroxyheptadecatrienoic acid (HHT, 22%) and thromboxane B2 (TXB2, 18%). The synthesis of eicosanoids was linear with the maturity of the macrophage subpopulations, suggesting that eicosanoid production is increased in in-vivo activated macrophages.

Phorbol esters stimulate a phospholipase D-catalysed reaction with both ester- and ether-linked phospholipids in HeLa cells.

The phorbol ester, 12-tetradecanoylphorbol-13-acetate (TPA), stimulated the accumulation of labelled phosphatidylethanol (PEth) in HeLa cells prelabelled with [3H]hexadecanol and incubated in the presence of ethanol. PEth formation involves a phospholipase D-catalysed phosphatidyl transferase reaction. [3H]Hexadecanol labelled both ester- and ether-derivatives of HeLa cell phospholipids and TPA stimulated the conversion of both classes of lipid to PEth.