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Interleukin 15 and 17 in Staphylococcus aureus arthritis

Doctoral thesis
Authors Louise Henningsson
Date of public defense 2011-11-24
ISBN 978-91-633-9569-7
Publication year 2011
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Language en
Keywords Staphylococcus aureus, Interleukin-17A, Interleukin-15, arthritis, osteoclasts, IL-23
Subject categories Medical and Health Sciences


Staphylococcus aureus–induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Thus, there is a need to identify new treatment targets in addition to antibiotic therapy. Interleukin (IL)-15 has been implicated both in osteoclastogenesis and in bacterial clearance – two important issues in S. aureus−induced joint destruction. Interleukin-17A has been discovered as an important mediator of aseptic arthritis both in mice and men, while its function in S. aureus–induced arthritis is largely unknown. The aim of this thesis was to investigate the importance of IL-15 and IL-17A and in addition, the interaction between IL-17A and interleukin-23 in S. aureus−induced arthritis. Wildtype, IL-15 knockout and IL-17A knockout mice were inoculated (systemically or locally) with a defined number of toxic shock syndrome toxin-1 (TSST-1) producing S. aureus. At sacrifice, tissues were collected and further analysed. We found that mice genetically lacking IL-15 or treated with anti-IL-15 antibodies developed less severe and destructive arthritis compared with control mice. In neither situation the bacterial clearance was negatively influenced. Furthermore, the IL-15 knockout mice had fewer osteoclasts in the joints compared with wildtype mice. We suggest that due to IL-15 absence, the mice developed milder arthritis probably because of less bone and cartilage destruction. We observed that IL-17A was of minor importance in systemic S. aureus arthritis but played a major role in local S. aureus arthritis. In the systemic model of arthritis we found elevated levels of IL-17F in the IL-17A knockout mice, suggesting that IL-17F compensates for the absence of IL-17A and that IL-17F in a normal wildtype mice is inhibited by IL-17A. Furthermore we found that IL-17A regulates the production of IL-23, a cytokine that is known to regulate the production of IL-17A, in a negative feedback manner, which means that IL-17A may have regulatory properties. Thus, we have found that IL-15, but not IL-17A, could represent a promising treatment target along with antibiotics in S. aureus−induced arthritis, and that IL-17A negatively regulates its upstream inducer, IL-23.

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