Antibiotics with Interleukin-15 inhibition reduces joint inflammation and bone erosions but not cartilage destruction in Staphylococcus aureus-induced arthritis

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
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 > Institute of Infection Immunity and Inflammation
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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