title: IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.
abstract: BACKGROUND
  Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.
  
  
  OBJECTIVE
  To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice.
  
  
  METHODS
  NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.
  
  
  RESULTS
  IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.
  
  
  CONCLUSIONS
  IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Abukar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Manli
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mattias N D
authors.initials: MN
authors.lastname: Svensson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Magnusson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Amanda
authors.initials: A
authors.lastname: Welin
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan-Christoph
authors.initials: JC
authors.lastname: Schwarze
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Majd
authors.initials: M
authors.lastname: Mohammad
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Rille
authors.initials: R
authors.lastname: Pullerits
authors.affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000382:microbiology; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007596:Joints / Q000473:pathology; D007668:Kidney / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013210:Staphylococcus; D013211:Staphylococcus aureus; D055114:X-Ray Microtomography
chemical_list: D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein