アルコールデヒドロゲネーゼに対する急性アルコール性肝炎と細胞のTh1免疫反応
Laura J Blackmore1, Jennifer M Ryan1, Xiaohong Huang1
1Institute of Liver Studies & Transplantation, King's College London, London, UK.
Lancet (London, England)
|August 28, 2015
まとめ
アルコール性肝炎患者はアルコール脱水素酶 (ADH) に対する免疫反応を示し,炎症誘発性Tヘルパー1型 (Th1) 反応は肝硬化患者より強い. これは,Th1免疫抑制がアルコール性肝炎の潜在的な治療法であることを示唆しています.
科学分野:
- 免疫学
- ヘパトロジー
- 胃腸内科
背景:
- アルコール性肝炎は重度の肝炎であり,死亡率は高い.
- 以前の研究では,アルコールによる肝硬変におけるアルコール脱水素酵素 (ADH) 固有の免疫反応が示された.
- アルコール性肝炎におけるADH特有の細胞免疫の存在は未定義のままである.
研究 の 目的:
- アルコール性肝炎の患者でADH特異的な細胞免疫が存在するかどうかを判断する.
- アルコール性肝炎における免疫反応と,アルコール性肝硬変および健康な対照群における免疫反応を比較する.
主な方法:
- 周辺血液単核細胞 (PBMC) は15人のアルコール性肝炎患者,9人の肝硬変患者,3人の健康な対照群から採取された.
- 人間のADHβ1サブユニットの25の重複ペプチドへのPBMC増殖は, (3H) - ティミジン組み込みで評価されました.
- インターフェロン・ガンマ (IFNγ),インターレウキン-17 (IL-17) およびIL-4の濃度はELISAを用いて測定された.
主要な成果:
- 15人のアルコール性肝炎患者のうち7人はADHペプチドに対する増殖反応を示した.
- 炎症性サイトカインであるIFNγとIL-17は,アルコール性肝炎患者のPBMCで検出されました.
- 肝硬変患者はADHペプチドの認識を示したが,アルコール性肝炎患者はTh1 (IFNγ) とTh17 (IL-17) の反応がより顕著であった.
結論:
- アルコール性肝炎における増殖性抗ADH免疫反応は,特定の表皮部に向けられる.
- 主要な炎症性Tヘルパー型1 (Th1) 免疫反応がアルコール性肝炎の特徴である.
- Th1免疫抑制を目的とした標的治療は,アルコール性肝炎の治療のための調査を正当化します.
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