PMID- 26252430
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20150824
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 34
IP  - 4
DP  - 2015 Oct
TI  - Protective effect of neutralizing anti-IL-18alpha monoclonal antibody on a mouse 
      model of acute graft-versus-host disease.
PG  - 2031-9
LID - 10.3892/or.2015.4176 [doi]
AB  - Graft-versus-host disease (GVHD) is a devastating complication of hematopoietic 
      stem cell transplantation (HSCT), and is characterized by systemic inflammation 
      and tissue damage in multiple organs, such as the liver and small intestine. 
      Interleukin-18 (IL-18), an important pro-inflammatory cytokine, is elevated 
      during the course of acute GVHD (aGVHD), and is associated with the severe 
      clinical manifestations of the disease. The biological activity of IL-18 is based 
      on its interaction with the IL-18 receptor (IL-18R) expressed in a variety of 
      cells. The aim of this study was to assess whether blocking the interaction of 
      IL-18 with IL-18R by the anti-IL‑18Ralpha antibody could attenuate the severity of 
      aGVHD. We used a well-established mouse bone marrow transplantation (BMT) model 
      (B6-->BALB/c) to block the IL-18/IL-18R interaction by a neutralizing monoclonal 
      antibody (mAb) against murine IL-18Ralpha. Administration of anti-IL-18Ralpha mAb had a 
      significant protective effect on the clinical and pathologic manifestations of 
      aGVHD, resulting in a markedly improved survival rate, modified inflammatory 
      response and decreased tissue damage. Interfering with IL-18/IL-18R interaction 
      affected levels of Th1, Th2 and Th17 subsets in the peripheral blood of the aGVHD 
      animals. Additionally, it led to decreased tissue expression of IL-18 and 
      apoptosis-associated molecules (Fas and FasL), and lower phosphorylation levels 
      of p38MAPK in the liver and small intestine. These changes coincided with the 
      decrease in cell apoptosis in aGVHD target organs. Thus, anti‑IL-18Ralpha therapy 
      may, therefore, represent a new therapeutic interference approach for treating 
      aGVHD.
FAU - Li, Xiaocui
AU  - Li X
AD  - Department of Pathogenic Biology and Immunology, Laboratory of Infection and 
      Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
FAU - Zhang, Cuiping
AU  - Zhang C
AD  - Department of Pathogenic Biology and Immunology, Laboratory of Infection and 
      Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
FAU - Chen, Wei
AU  - Chen W
AD  - Blood Diseases Institute, Xuzhou Medical College; Key Laboratory of Bone Marrow 
      Stem Cells; Department of Hematology, The Affiliated Hospital of Xuzhou Medical 
      College, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Pan, Bin
AU  - Pan B
AD  - Blood Diseases Institute, Xuzhou Medical College; Key Laboratory of Bone Marrow 
      Stem Cells; Department of Hematology, The Affiliated Hospital of Xuzhou Medical 
      College, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Kong, Fanyun
AU  - Kong F
AD  - Department of Pathogenic Biology and Immunology, Laboratory of Infection and 
      Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
FAU - Zheng, Kuiyang
AU  - Zheng K
AD  - Department of Pathogenic Biology and Immunology, Laboratory of Infection and 
      Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
FAU - Tang, Renxian
AU  - Tang R
AD  - Department of Pathogenic Biology and Immunology, Laboratory of Infection and 
      Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China.
FAU - Zeng, Lingyu
AU  - Zeng L
AD  - Blood Diseases Institute, Xuzhou Medical College; Key Laboratory of Bone Marrow 
      Stem Cells; Department of Hematology, The Affiliated Hospital of Xuzhou Medical 
      College, Xuzhou, Jiangsu 221002, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150805
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/therapeutic use
MH  - Antibodies, Neutralizing/*administration & dosage/therapeutic use
MH  - Disease Models, Animal
MH  - Graft vs Host Disease/*drug therapy/immunology/metabolism
MH  - Humans
MH  - Interleukin-18/*metabolism
MH  - Interleukin-18 Receptor alpha Subunit/*antagonists & inhibitors/metabolism
MH  - Intestine, Small/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Survival Analysis
MH  - T-Lymphocytes, Helper-Inducer/metabolism
EDAT- 2015/08/08 06:00
MHDA- 2016/05/25 06:00
CRDT- 2015/08/08 06:00
PHST- 2015/04/07 00:00 [received]
PHST- 2015/06/24 00:00 [accepted]
PHST- 2015/08/08 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
AID - 10.3892/or.2015.4176 [doi]
PST - ppublish
SO  - Oncol Rep. 2015 Oct;34(4):2031-9. doi: 10.3892/or.2015.4176. Epub 2015 Aug 5.