Effects of antibiotics on expression and function of Toll-like receptors 2 and 4 on mononuclear cells in patients with advanced cirrhosis
| Autor: | Narelle A Skinner, Vesna Markovska, Adam G Testro, Paul J Gow, Peter W Angus, Kumar Visvanathan, Sarah Wongseelashote |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Liver Cirrhosis Male medicine.drug_class Antibiotics Biology In Vitro Techniques Peritonitis Immune system Spontaneous bacterial peritonitis Trimethoprim Sulfamethoxazole Drug Combination medicine Humans Antibiotic prophylaxis Antibacterial agent Aged Toll-like receptor Hepatology Tumor Necrosis Factor-alpha Middle Aged medicine.disease Immunity Innate Toll-Like Receptor 2 Anti-Bacterial Agents Toll-Like Receptor 4 TLR2 Case-Control Studies Immunology TLR4 Leukocytes Mononuclear Female Gram-Negative Bacterial Infections Norfloxacin |
| Zdroj: | Journal of hepatology. 52(2) |
| ISSN: | 1600-0641 |
| Popis: | Background & Aims 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. Methods 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-α production measured. Results 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-α production increased following antibiotic use (1077 vs. 3620pg/mL, p Conclusions 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. |
| Databáze: | OpenAIRE |
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