Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis
AuthorRiordan, SM; Skinner, N; Nagree, A; McCallum, H; McIver, CJ; Kurtovic, J; Hamilton, JA; Bengmark, S; Williams, R; Visvanathan, K
AffiliationPaediatrics Royal Children'S Hospital
Document TypeJournal Article
CitationsRiordan, S. M., Skinner, N., Nagree, A., McCallum, H., McIver, C. J., Kurtovic, J., Hamilton, J. A., Bengmark, S., Williams, R. & Visvanathan, K. (2003). Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis. HEPATOLOGY, 37 (5), pp.1154-1164. https://doi.org/10.1053/jhep.2003.50180.
Access StatusThis item is currently not available from this repository
C1 - Journal Articles Refereed
Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor alpha (TNF-alpha) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll-like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF-alpha in response to endotoxin and Gram-positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF-alpha, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF-alpha production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF-alpha levels, and in vitro TNF-alpha production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram-positive bacteria. Endotoxin, TNF-alpha, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up-regulated in cirrhosis and correlated significantly with serum TNF-alpha and sTNFR levels. In vitro TNF-alpha production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up-regulation of PBMC expression of TLR2. Serum TNF-alpha levels were further increased and in vitro TNF-alpha production further reduced in most patients. In conclusion, up-regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram-positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF-alpha and sTNFR levels in cirrhosis.
KeywordsAllergy; Gastroenterology and Hepatology; Immune System and Allergy; Digestive System Disorders
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References