Bergmann, B., Jirholt, P., Henning, P., Lindholm, C., Ohlsson, C., McInnes, I. B. , Lerner, U. H. and Gjertsson, I. (2018) Antibiotics with Interleukin-15 inhibition reduces joint inflammation and bone erosions but not cartilage destruction in Staphylococcus aureus-induced arthritis. Infection and Immunity, 86(5), e00960-17. (doi: 10.1128/IAI.00960-17) (PMID:29440371)
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Abstract
Background: Staphylococcus aureus-induced arthritis causes rapid joint destruction, often leading to disabling joint damage despite antibiotics. We have previously shown that IL-15 inhibition without antibiotics is beneficial in S. aureus-induced arthritis. We therefore hypothesized that inhibition of IL-15, in combination with antibiotics, might represent a useful therapy that would both reduce inflammation and joint destruction, but preserve the host's ability to clear the infection. Methods: Female wildtype C57BL/6 mice were intravenously inoculated with the TSST-1-producing LS-1 strain of S. aureus with 0.8x108 S. aureus LS-1/mouse. Three days later the treatment was started consisting of cloxacillin followed by flucloxacillin, together with either anti-IL-15 antibodies (aIL-15ab) or control antibodies. Outcomes included survival, weight change, bacterial clearance, and joint damage. Results: The addition of aIL-15ab to antibiotics in S. aureus-induced arthritis reduced synovitis and bone erosions compared to controls. The number of bone-resorbing osteoclasts in the joints was reduced, whereas cartilage destruction was not significantly altered. Importantly, the combination therapy did not adversely affect the clinical outcome of S. aureus-induced arthritis, such as survival, weight change or compromise the host's ability to clear the infection. Conclusions: As the clinical outcome of S. aureus-induced arthritis was not affected, the addition of aIL-15ab to antibiotics ought to be safe. Taken together, the combination of aIL-15ab and antibiotics is a beneficial, but not optimal, treatment of S. aureus-induced arthritis as it reduces synovitis and bone erosions but has a limited effect on cartilage destruction.
Item Type: | Articles |
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Additional Information: | Funding sources are Göteborg Medical Society, Swedish Science Research Council, Torsten and Ragnar Söderbergs Stiftelse, Reumatikerförbundet (The Swedish Rheumatism Association), King Gustav V Stiftelse, IngaBritt och Arne Lundbergs Stiftelse, Lundgrens Stiftelse, Amlövs Stiftelse, and Swedish Medical Society. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain |
Authors: | Bergmann, B., Jirholt, P., Henning, P., Lindholm, C., Ohlsson, C., McInnes, I. B., Lerner, U. H., and Gjertsson, I. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Infection and Immunity |
Publisher: | American Society for Microbiology |
ISSN: | 0019-9567 |
ISSN (Online): | 1098-5522 |
Published Online: | 12 February 2018 |
Copyright Holders: | Copyright © 2018 Bergmann et al. |
First Published: | First published in Infection and Immunity 86(5):e00960-17 |
Publisher Policy: | Reproduced under a Creative Commons License |
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