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Title: Effects of antibiotics on expression and function of Toll-like receptors 2 and 4 on mononuclear cells in patients with advanced cirrhosis.
Austin Authors: Testro, Adam G ;Gow, Paul J ;Angus, Peter W ;Wongseelashote, Sarah;Skinner, Narelle;Markovska, Vesna;Visvanathan, Kumar
Affiliation: Medicine (University of Melbourne)
Issue Date: 16-Dec-2009
Publication information: Journal of Hepatology 2009; 52(2): 199-205
Abstract: Toll-like receptors (TLRs) are critical to innate immune responses. TLR4 recognises Gram-negative bacteria, whilst TLR2 recognises Gram-positive. We examined TLR expression and function in cirrhosis, and whether this is affected by antibiotic therapy.Sixty-four subjects were included (23 controls and 41 Child-Pugh C cirrhotic patients). Thirty patients were taking norfloxacin or trimethoprim-sulfamethoxazole as prophylaxis against bacterial peritonitis and 11 were not. In a second study, 8 patients were examined before and after commencement of antibiotics. Monocyte expression of TLR2 and 4 was determined by flow cytometry. Monocytes from the patients with paired samples were stimulated using TLR ligands and TNF-alpha production measured.Patients not taking antibiotics had significantly decreased TLR4 expression compared with controls (0.74 vs. 1.0, p=0.009) and patients receiving antibiotics (0.74 vs. 0.98, p=0.02). There were no differences with regard to TLR2. In the patients with paired samples, TLR4 expression increased (0.74-1.49, p=0.002) following antibiotic use, whilst again, there was no change in TLR2 expression (0.99 vs. 0.92, p=0.20). TLR4-dependent TNF-alpha production increased following antibiotic use (1077 vs. 3620pg/mL, p<0.05), whilst TLR2-dependent production was unchanged.TLR4 expression is decreased in patients with Child-Pugh C cirrhosis, but is restored by antibiotics targeting enteric Gram-negative bacteria. TLR4-dependent cytokine production also increases significantly following antibiotic therapy. This suggests that the high incidence of Gram-negative infection in cirrhotic patients is in part due to down-regulation of the TLR4-dependant immune response and that the efficacy of antibiotic prophylaxis is contributed to by modulation of innate immunity.
DOI: 10.1016/j.jhep.2009.11.006
Journal: Journal of Hepatology
Type: Journal Article
Subjects: Adult
Anti-Bacterial Agents.pharmacology
Case-Control Studies
Gram-Negative Bacterial Infections.prevention & control
Immunity, Innate.drug effects
In Vitro Techniques
Leukocytes, Mononuclear.drug effects.immunology
Liver Cirrhosis.drug therapy.immunology
Middle Aged
Peritonitis.prevention & control
Toll-Like Receptor 2.metabolism
Toll-Like Receptor 4.metabolism
Trimethoprim-Sulfamethoxazole Combination.pharmacology
Tumor Necrosis Factor-alpha.biosynthesis
Appears in Collections:Journal articles

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