CTLA4 Immunoglobulin but Not Anti-Tumor Necrosis Factor Therapy Promotes Staphylococcal Septic Arthritis in Mice

被引：34

作者：

Ali, Abukar ^{[1
]}

Welin, Amanda ^{[1
]}

Schwarze, Jan-Christoph ^{[1
]}

Svensson, Mattias N. D. ^{[1
]}

Na, Manli ^{[1
]}

Jarneborn, Anders ^{[1
]}

Magnusson, Malin ^{[1
]}

Mohammad, Majd ^{[1
]}

Kwiecinski, Jakub ^{[1
]}

Josefsson, Elisabet ^{[1
]}

Bylund, Johan ^{[1
]}

Pullerits, Rille ^{[1
]}

Jin, Tao ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, S-41346 Gothenburg, Sweden

来源：

JOURNAL OF INFECTIOUS DISEASES | 2015年 / 212卷 / 08期

基金：

英国医学研究理事会;

关键词：

Staphylococcus aureus; septic arthritis; mouse; abatacept; etanercept; RHEUMATOID-ARTHRITIS; T-CELLS; ALPHA ANTAGONISTS; AUREUS ARTHRITIS; RISK-FACTORS; TNF-ALPHA; TGF-BETA; INFECTIONS; SEPSIS; ABATACEPT;

D O I：

10.1093/infdis/jiv212

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. The development of biologics has greatly increased the quality of life and the life expectancy of many patients with rheumatoid arthritis. However, a large number of these patients have an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-tumor necrosis factor (TNF) treatment and CTLA4 immunoglobulin (Ig) treatment on both immunological response and host defense in a murine model of septic arthritis. Methods. Abatacept (CTLA4-Ig), etanercept (anti-TNF), or phosphate-buffered saline were given to NMRI mice intravenously inoculated with Staphylococcus aureus. The clinical course of septic arthritis and histopathological and radiological changes of joints were compared among the groups. Results. Mice receiving CTLA4-Ig treatment had more-severe septic arthritis, compared with controls and mice receiving anti-TNF treatment. Anti-TNF treatment led to more-severe weight loss and kidney abscesses, as well as a higher bacterial burden in the kidneys. Mice receiving CTLA4-Ig therapy had lower serum levels of interleukin 4, whereas mice receiving anti-TNF therapy had higher levels of TNF-alpha. Both iNOS and arginase-1 expression were reduced in peritoneal macrophages from mice receiving CTLA4-Ig, compared with expression in the anti-TNF group. Conclusions. CTLA4-Ig therapy significantly increased the susceptibility to S. aureus septic arthritis in mice, whereas anti-TNF therapy deteriorated host bacterial clearance, resulting in more-severe weight loss and kidney abscesses.

引用

页码：1308 / 1316

页数：9

共 37 条

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