Excessive In Vitro Bacterial Lipopolysaccharide–Induced Production of Monokines in Cirrhosis

Abstract

The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of inflammatory cytokines by peripheral blood monocytes in chronic alcoholism: Relationship with ethanol intake and liver disease

“…Reported studies show that ALC is associated with depressed secretion of IL1 (27,48,49) and TNFa (27,49) by both LPS-stimulated PB monocytes (27) and macrophages (49), which is even more pronounced among patients with severe ALC and malnutrition (48,49). In contrast, others have found an increased secretion of IL1 (50) and TNFa (50,51) by LPS-stimulated PB monocytes from ALC patients. Additionally, a close relationship between severity of ALC (Child-Pough score B or C) and the elevation of the expression of both the TNF and TNF-receptor genes in PB mononuclear cells has been observed (52).…”

Pulmonary Edema in Patients After Liver Transplantation

“…The development of less severe degrees of pulmonary edema may result from poor immune function 14,15 and increased levels of proinflammatory mediators. 16,17 Malnutrition may also be important, although it has been shown that pulmonary edema may occur in patients with liver dysfunction despite correction of vascular oncotic pressures. 18 In our study, no patient had radiological evidence of interstitial pulmonary edema preoperatively.…”

Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

“…It has been shown that PBMCs from patients with cirrhosis after resting in vitro for 24 hours produce TNF-␣ levels similar to those of healthy controls. 26 It may be that this primed state in patients with cirrhosis may overcome the proposed mechanism of inhibition by calcineurin inhibitors. The inhibition of TNF-␣ production by dexamethasone is likely to be a different mechanism unaffected by liver disease.…”