The therapeutic effect of TNFR1-selective antagonistic mutant TNF-alpha in murine hepatitis models
| Autor: | Shin-ichi Tsunoda, Yasuhiro Abe, Hiroko Shibata, Tetsuya Nomura, Shinsaku Nakagawa, Yohei Mukai, Haruhiko Kamada, Yasuo Yoshioka, Tsunetaka Ohta, Yasuo Tsutsumi, Madoka Taniai, Tadanori Mayumi, Akiko Ohkawa |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Immunology
Inflammation Pharmacology Hepatitis Animal Biochemistry Cell Line Mice Immune system medicine Concanavalin A Immunology and Allergy Animals Humans Receptor Molecular Biology Carbon Tetrachloride Hepatitis Mice Inbred BALB C biology business.industry Tumor Necrosis Factor-alpha Biological activity Alanine Transaminase Hematology medicine.disease In vitro Disease Models Animal Receptors Tumor Necrosis Factor Type I biology.protein Cytokines Tumor necrosis factor alpha Female medicine.symptom business |
| Zdroj: | Cytokine. 44(2) |
| ISSN: | 1096-0023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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