title: CTLA4 Immunoglobulin but Not Anti-Tumor Necrosis Factor Therapy Promotes Staphylococcal Septic Arthritis in Mice.
abstract: 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.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Abukar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Amanda
authors.initials: A
authors.lastname: Welin
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Jan-Christoph
authors.initials: JC
authors.lastname: Schwarze
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Mattias N D
authors.initials: MN
authors.lastname: Svensson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Jarneborn
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Magnusson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Majd
authors.initials: M
authors.lastname: Mohammad
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwiecinski
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Rille
authors.initials: R
authors.lastname: Pullerits
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D007596:Joints / Q000276:immunology / Q000473:pathology; D051379:Mice; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; D000068800:Etanercept
keywords: Staphylococcus aureus; abatacept; etanercept; mouse; septic arthritis