PMID- 18815054
OWN - NLM
STAT- MEDLINE
DCOM- 20090114
LR  - 20131121
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 44
IP  - 2
DP  - 2008 Nov
TI  - The therapeutic effect of TNFR1-selective antagonistic mutant TNF-alpha in murine 
      hepatitis models.
PG  - 229-33
LID - 10.1016/j.cyto.2008.07.003 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is critically involved in a wide variety 
      of inflammatory pathologies, such as hepatitis, via the TNF receptor-1 (TNFR1). 
      To develop TNFR1-targeted anti-inflammatory drugs, we have already succeeded in 
      creating a TNFR1-selective antagonistic mutant TNF-alpha (R1antTNF) and shown 
      that R1antTNF efficiently inhibits TNF-alpha/TNFR1-mediated biological activity 
      in vitro. In this study, we examined the therapeutic effect of R1antTNF in acute 
      hepatitis using two independent experimental models, induced by carbon 
      tetrachloride (CCl(4)) or concanavalin A (ConA). In a CCl(4)-induced model, 
      treatment with R1antTNF significantly inhibited elevation in the serum level of 
      ALT (alanine aminotransferase), a marker for liver damage. In a ConA-induced 
      T-cell-mediated hepatitis model, R1antTNF also inhibited the production of serum 
      immune activated markers such as IL-2 and IL-6. These R1antTNF-mediated 
      therapeutic effects were as good as or better than those obtained using 
      conventional anti-TNF-alpha antibody therapy. Our results suggest that R1antTNF 
      may be a clinically useful TNF-alpha antagonist in hepatitis.
FAU - Shibata, Hiroko
AU  - Shibata H
AD  - Laboratory of Pharmaceutical Proteomics, National Institute of Biomedical 
      Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
FAU - Yoshioka, Yasuo
AU  - Yoshioka Y
FAU - Ohkawa, Akiko
AU  - Ohkawa A
FAU - Abe, Yasuhiro
AU  - Abe Y
FAU - Nomura, Tetsuya
AU  - Nomura T
FAU - Mukai, Yohei
AU  - Mukai Y
FAU - Nakagawa, Shinsaku
AU  - Nakagawa S
FAU - Taniai, Madoka
AU  - Taniai M
FAU - Ohta, Tsunetaka
AU  - Ohta T
FAU - Mayumi, Tadanori
AU  - Mayumi T
FAU - Kamada, Haruhiko
AU  - Kamada H
FAU - Tsunoda, Shin-ichi
AU  - Tsunoda S
FAU - Tsutsumi, Yasuo
AU  - Tsutsumi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080923
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11028-71-0 (Concanavalin A)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Carbon Tetrachloride/pharmacology
MH  - Cell Line
MH  - Concanavalin A/pharmacology
MH  - Cytokines/blood
MH  - Disease Models, Animal
MH  - Female
MH  - Hepatitis, Animal/blood/chemically induced/*drug therapy/immunology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*therapeutic use
EDAT- 2008/09/26 09:00
MHDA- 2009/01/15 09:00
CRDT- 2008/09/26 09:00
PHST- 2008/04/23 00:00 [received]
PHST- 2008/07/01 00:00 [revised]
PHST- 2008/07/14 00:00 [accepted]
PHST- 2008/09/26 09:00 [pubmed]
PHST- 2009/01/15 09:00 [medline]
PHST- 2008/09/26 09:00 [entrez]
AID - S1043-4666(08)00199-3 [pii]
AID - 10.1016/j.cyto.2008.07.003 [doi]
PST - ppublish
SO  - Cytokine. 2008 Nov;44(2):229-33. doi: 10.1016/j.cyto.2008.07.003. Epub 2008 Sep 
      23.