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Toll-like receptor expression in chronic hepatitis C: Correlation with pro-inflammatory cytokine levels and liver injury.

Riordan, SM; Skinner, NA; Kurtovic, J; Locarnini, S; McIver, CJ; Williams, R; (2006) Toll-like receptor expression in chronic hepatitis C: Correlation with pro-inflammatory cytokine levels and liver injury. Inflammation Research , 55 (7) 279 - 285.

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Abstract

Background/Aims Toll-like receptors (TLR’s) are critical receptors that promote innate immune responses to pathogen-associated molecular patterns. Activation of TLR’s leads to production of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α. This study investigates whether peripheral blood monocyte expression of TLR’s is disturbed in patients with chronic hepatitis C and whether levels of expression of these molecules are significantly correlated with hepatitis C virus (HCV) genotype, viral load, hepatic necroinflammatory activity, histological stage and circulating TNF-α concentrations. Methods In 18 non-cirrhotic patients with biopsy-proven, virologically-confirmed chronic hepatitis C and 32 controls, we measured expression of TLR2 and TLR4 on peripheral blood monocytes. HCV genotype, viral load, serum alanine aminotransferase (ALT) levels, histological stage of disease and circulating TNF-α and endotoxin levels were also determined. Results Peripheral blood monocyte expression of TLR2 and TLR4 were significantly increased in patients with chronic hepatitis C compared to controls, irrespective of HCV genotype or histological stage of disease. Circulating levels of TNF-α were also significantly increased in patients with chronic hepatitis C. In both the overall study cohort and patients with chronic hepatitis C, monocyte expression of TLR2, but not of TLR4, correlated significantly with serum TNF-α levels. In patients with chronic hepatitis C, monocyte expression of TLR2, but not of TLR4, also correlated significantly with serum ALT levels. Expression of TLR’s was not significantly correlated with viral load. Conclusions Up-regulation of peripheral blood monocyte expression of TLR2 and TLR4 occurs in patients with chronic hepatitis C. Increased monocyte expression of TLR2, but not of TLR4, correlates significantly with both increased circulating TNF-α levels and hepatic necroinflammatory activity in this disorder.

Type:Article
Title:Toll-like receptor expression in chronic hepatitis C: Correlation with pro-inflammatory cytokine levels and liver injury.
Keywords:Toll-like receptors, Hepatitis C virus

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