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-α. 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.
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-α. 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.
Authors: Michelle Schultz; Majd Mohammad; Minh-Thu Nguyen; Zhicheng Hu; Anders Jarneborn; Carina M Wienken; Matti Froning; Rille Pullerits; Abukar Ali; Heiko Hayen; Friedrich Götz; Tao Jin Journal: Front Microbiol Date: 2022-03-09 Impact factor: 5.640
Authors: Abukar Ali; Manli Na; Mattias N D Svensson; Malin Magnusson; Amanda Welin; Jan-Christoph Schwarze; Majd Mohammad; Elisabet Josefsson; Rille Pullerits; Tao Jin Journal: PLoS One Date: 2015-07-02 Impact factor: 3.240
Authors: Majd Mohammad; Manli Na; Amanda Welin; Mattias N D Svensson; Abukar Ali; Tao Jin; Rille Pullerits Journal: PLoS One Date: 2016-12-01 Impact factor: 3.240
Authors: Farah Fatima; Ying Fei; Abukar Ali; Majd Mohammad; Malin C Erlandsson; Maria I Bokarewa; Muhammad Nawaz; Hadi Valadi; Manli Na; Tao Jin Journal: PLoS One Date: 2017-02-02 Impact factor: 3.240