PMID- 27214392
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20180209
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 36
IP  - 12
DP  - 2016 Dec
TI  - Selective intestinal decontamination with norfloxacin enhances a regulatory T 
      cell-mediated inflammatory control mechanism in cirrhosis.
PG  - 1811-1820
LID - 10.1111/liv.13172 [doi]
AB  - BACKGROUND & AIMS: Norfloxacin exerts immunomodulatory effects in cirrhosis 
      beyond its bactericidal activity. We aimed at identifying the role of regulatory 
      T (Treg) cells in the norfloxacin mechanism that compensates the inflammatory 
      environment in cirrhosis. PATIENTS & METHODS: Consecutively admitted patients 
      with cirrhosis and ascitic fluid (AF) with: spontaneous bacterial peritonitis 
      (SBP), non-infected AF, and norfloxacin as secondary SBP prophylaxis (SID group). 
      Tregs were defined by flow-cytometry as CD4(+) CD25(+) FoxP3(+) cells. Dendritic 
      cells (DCs) were purified for co-stimulatory signalling evaluation and 
      norfloxacin and IL-10 levels were measured in serum. Wildtype and recombination 
      activating gene 1 (Rag1)-deficient mice with CCl(4) -induced cirrhosis were used 
      for adoptive-transfer experiments using naive CD4(+) T cells and Tregs. RESULTS: 
      Eighty-four patients were included. Treg percentage was significantly increased 
      in SID patients compared with SBP or non-infected AF patients. A positive 
      correlation was observed between Tregs and serum norfloxacin and IL-10 levels. 
      DCs from SID patients showed a significantly decreased expression of CD80 and 
      CD86 compared with SBP and non-infected AF patients and correlated with 
      norfloxacin levels. Modulation of co-stimulatory signalling by norfloxacin was 
      not detected in Rag1-deficient mice and Rag1-deficient mice reconstituted with 
      naive T-cells. However, reconstitution with naive T-cells and Tregs was 
      associated with significantly downregulated CD80 and CD86 expression in the 
      presence of norfloxacin. Norfloxacin immunomodulatory effect on IL-2 and 
      IFN-gamma reduction and on the increase of IL-10 was significantly achieved only 
      when the Tregs were restored in Rag1-deficient mice. CONCLUSIONS: These results 
      provide a plausible mechanism for the immunomodulatory effects of norfloxacin in 
      cirrhosis beyond its bactericidal effect.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Juanola, Oriol
AU  - Juanola O
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
AD  - Departamento Medicina Clinica, Universidad Miguel Hernandez, San Juan de 
      Alicante, Spain.
FAU - Gomez-Hurtado, Isabel
AU  - Gomez-Hurtado I
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
FAU - Zapater, Pedro
AU  - Zapater P
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL-Fundacion 
      FISABIO), Alicante, Spain.
FAU - Moratalla, Alba
AU  - Moratalla A
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
FAU - Caparros, Esther
AU  - Caparros E
AD  - Departamento Medicina Clinica, Universidad Miguel Hernandez, San Juan de 
      Alicante, Spain.
FAU - Pinero, Paula
AU  - Pinero P
AD  - Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL-Fundacion 
      FISABIO), Alicante, Spain.
FAU - Gonzalez-Navajas, Jose M
AU  - Gonzalez-Navajas JM
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL-Fundacion 
      FISABIO), Alicante, Spain.
FAU - Gimenez, Paula
AU  - Gimenez P
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
FAU - Such, Jose
AU  - Such J
AD  - Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates.
FAU - Frances, Ruben
AU  - Frances R
AD  - CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
AD  - Departamento Medicina Clinica, Universidad Miguel Hernandez, San Juan de 
      Alicante, Spain.
AD  - Instituto de Investigacion Sanitaria y Biomedica de Alicante (ISABIAL-Fundacion 
      FISABIO), Alicante, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160621
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (IL10 protein, human)
RN  - 0 (IL2 protein, human)
RN  - 0 (Interleukin-2)
RN  - 130068-27-8 (Interleukin-10)
RN  - N0F8P22L1P (Norfloxacin)
SB  - IM
MH  - Adoptive Transfer
MH  - Aged
MH  - Animals
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - B7-1 Antigen/metabolism
MH  - B7-2 Antigen/metabolism
MH  - Bacterial Infections/*drug therapy
MH  - Bacterial Translocation/*drug effects
MH  - Dendritic Cells/drug effects
MH  - Female
MH  - Forkhead Transcription Factors/metabolism
MH  - Humans
MH  - Interleukin-10/blood
MH  - Interleukin-2/blood
MH  - Liver Cirrhosis/*complications/microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Norfloxacin/*therapeutic use
MH  - Peritonitis/*drug therapy/microbiology
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology
OTO - NOTNLM
OT  - bacterial translocation
OT  - cirrhosis
OT  - norfloxacin
OT  - regulatory T cells
EDAT- 2016/05/24 06:00
MHDA- 2017/11/01 06:00
CRDT- 2016/05/24 06:00
PHST- 2016/03/14 00:00 [received]
PHST- 2016/05/18 00:00 [accepted]
PHST- 2016/05/24 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2016/05/24 06:00 [entrez]
AID - 10.1111/liv.13172 [doi]
PST - ppublish
SO  - Liver Int. 2016 Dec;36(12):1811-1820. doi: 10.1111/liv.13172. Epub 2016 Jun 21.