Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

被引：24

作者：

Pech, T. ^{[1
]}

Finger, T. ^{[1
]}

Fujishiro, J. ^{[1
]}

Praktiknjo, M. ^{[1
]}

Ohsawa, I. ^{[1
]}

Abu-Elmagd, K. ^{[2
]}

Limmer, A. ^{[3
]}

Hirner, A. ^{[1
]}

Kalff, J. C. ^{[1
]}

Schaefer, N. ^{[1
]}

机构：

[1] Univ Bonn, Dept Surg, D-5300 Bonn, Germany

[2] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Div Intestinal Transplantat, Pittsburgh, PA 15260 USA

[3] Univ Bonn, IMMEI, D-5300 Bonn, Germany

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2010年 / 10卷 / 11期

关键词：

Acute rejection; motility; small bowel transplantation; TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE DYSFUNCTION; SMALL-BOWEL TRANSPLANTATION; FACTOR-ALPHA; ALLOGRAFT-REJECTION; TNF-ALPHA; ISCHEMIA/REPERFUSION INJURY; ANTIINFLAMMATORY ACTIVITY; RESIDENT MACROPHAGES; GRAFT MUSCULARIS;

D O I：

10.1111/j.1600-6143.2010.03279.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

As we have shown in the past, acute rejection-related TNF-alpha upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-alpha antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin (R) revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-gamma (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.

引用

页码：2431 / 2441

页数：11

共 47 条

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