title: Critical role of signaling through IL-1 receptor for development of arthritis and sepsis during Staphylococcus aureus infection.
abstract: IL-1R-deficient mice (IL-1R(-/-)) and their wild-type controls (IL-1R(+/+)) were i.v. inoculated with 1 x 10(7) or 10(6) Staphylococcus aureus per mouse to mimic bacterial sepsis and septic arthritis. The disease outcome was severely worsened in the IL-1R(-/-) mice as compared with IL-1R(+/+) mice. Indeed, 3 days after inoculation of 10(7) S. aureus per mouse 84% of IL-1R(-/-) mice displayed clinical signs of septicemia as compared with none of the IL-1R(+/+) mice. On day 9 after inoculation with 10(6) S. aureus per mouse 75% of the IL-1R(-/-) mice were dead as compared with none of the IL-1R(+/+) mice. Also, the number of staphylococci in circulation was 25- to 30-fold increased in IL-1R(-/-) mice as compared with IL-1R(+/+) mice, the most probable reason for the outcome. The frequency and severity of septic arthritis were significantly increased in IL-1R(-/-) mice, as compared with IL-1R(+/+) mice, following i.v. inoculation of staphylococci. This was probably due to an increased accumulation of bacteria in the joints of IL-1R(-/-) mice as compared with their wild-type controls. Interestingly, while serum levels of IL-18 in IL-1R(-/-) mice were significantly lower than in IL-1R(+/+) mice 24 h after inoculation of S. aureus, both IL-18 and IL-1beta were significantly increased in IL-1R(-/-) vs IL-1R(+/+) mice 4 days after the bacterial inoculation. In conclusion, IL-1R signaling plays a crucial role in host protection during systemic S. aureus infection as seen by the fatal outcome of S. aureus sepsis and arthritis in IL-1R-deficient mice.
authors: Department of Rheumatology, Göteborg University, Guldhedsgatan 10A, S-413 46 Göteborg, Sweden. olof.hultgren@immuno.gu.se
authors: Olof H
authors: OH
authors: Hultgren
authors: Lena
authors: L
authors: Svensson
authors: Andrej
authors: A
authors: Tarkowski
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology*; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha