Interleukin 15 mediates joint destruction in Staphylococcus aureus arthritis

J Infect Dis. 2012 Sep 1;206(5):687-96. doi: 10.1093/infdis/jis295. Epub 2012 Apr 16.

Abstract

Background: Staphylococcus aureus arthritis causes severe and rapid joint damage despite antibiotics. Thus, there is a need to identify new treatment targets in addition to antibiotics. Lately, interleukin 15 (IL-15) has been implicated both in osteoclastogenesis and in bacterial clearance-2 important issues in S. aureus-induced joint destruction. This has prompted us to investigate the importance of IL-15 in S. aureus-induced arthritis.

Methods: Toxic shock syndrome toxin-1 producing S. aureus was intravenously inoculated in IL-15 knockout and wildtype mice and in wildtype mice treated with anti-IL-15 antibodies (aIL-15ab) or isotype control antibody.

Results: Absence of IL-15, either in knockout mice or after treatment with aIL-15ab, significantly reduced weight loss compared with controls during the infection. The severity of synovitis and joint destruction was significantly decreased in IL-15 knockout and aIL-15ab treated mice compared with controls. In IL-15 knockout mice there was a reduced number of osteoclasts in the joints. The host's ability to clear bacteria was not influenced in the IL-15 knockout mice, but significantly increased after treatment with aIL-15ab.

Conclusions: IL-15 is a mediator of joint destruction in S. aureus-induced arthritis and contributes to general morbidity, which makes this cytokine an interesting treatment target in addition to conventional antibiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Arthritis, Infectious / immunology*
  • Arthritis, Infectious / microbiology*
  • Female
  • Gene Knockout Techniques
  • Histocytochemistry
  • Interleukin-15 / blood
  • Interleukin-15 / deficiency
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Joints / immunology*
  • Joints / microbiology
  • Joints / pathology
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoclasts / enzymology
  • Osteoclasts / immunology
  • Osteoclasts / pathology
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / isolation & purification*

Substances

  • Antibodies, Bacterial
  • Interleukin-15