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

Artikel i vetenskaplig tidskrift
Författare Berglind Bergmann
Pernilla Jirholt
Petra Henning
Catharina Lindholm
Claes Ohlsson
Iain B McInnes
Ulf H Lerner
Inger Gjertsson
Publicerad i Infection and immunity
Volym 86
Nummer/häfte 5
Sidor e00960-17
ISSN 1098-5522
Publiceringsår 2018
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Centre for Bone and Arthritis Research
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor e00960-17
Språk en
Länkar dx.doi.org/10.1128/IAI.00960-17
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Reumatologi och inflammation, Infektionsmedicin

Sammanfattning

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 0.8x108S. 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.

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