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Norfloxacin Modulates the Inflammatory Response and Directly Affects Neutrophils in Patients With Decompensated Cirrhosis
- Source :
- Gastroenterology. 137:1669-1679.e1
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels, probably because of a combined effect of norfloxacin on bowel flora and neutrophils.Thirty-one patients with cirrhosis receiving norfloxacin (400 mg/day) were included. Blood samples were collected at 0.5-4 hours (peak samples group, n = 47) and at 22-24 hours (trough samples group, n = 84) after dose. Fifty-nine ascitic fluid samples were obtained. Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients, respectively, (temporal profile group) and samples were collected at 0, 0.5, 1, 1.5, 2, 4, and 24 hours. Norfloxacin, trimethoprim/sulfamethoxazole, cytokines, nitric oxide, expression levels of nuclear factor (NF)-kappaB and inhibitor of NF-kappaB (IkB-alpha), neutrophil oxidative burst, and rate of apoptotic events were determined.All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide. Serum and ascitic levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-12, and nitric oxide were significantly lower in peak than in trough samples. A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha (r = -0.68; P.001), interferon-gamma (r = -0.66; P.001), interleukin-12 (r = -0.66; P.001), and nitric oxide (r = -0.68; P.001). Serum norfloxacin's highest concentrations (1 +/- 0.5 microg/mL) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide. Intracellular norfloxacin's highest levels (2 +/- 1 microg/mL/10(7) cells) were observed at 2 hours and concurred with a lower NF-kappaB expression, a reduced anion superoxide generation, and apoptotic rate in response to phorbol myristate acetate. Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression.Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis.
- Subjects :
- Liver Cirrhosis
Male
Cirrhosis
Lipopolysaccharide
Peritonitis
Pharmacology
Neutrophil Activation
Nitric oxide
Cohort Studies
chemistry.chemical_compound
Spontaneous bacterial peritonitis
medicine
Humans
Norfloxacin
Aged
Respiratory Burst
Cross-Over Studies
Hepatology
business.industry
Sulfamethoxazole
NF-kappa B
Gastroenterology
Bacterial Infections
Middle Aged
medicine.disease
Trimethoprim
Anti-Bacterial Agents
chemistry
Immunology
Cytokines
Female
Tumor necrosis factor alpha
business
medicine.drug
Subjects
Details
- ISSN :
- 00165085
- Volume :
- 137
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi.dedup.....bcb9f86c193d56913feef8c7aeb091bb