Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis

Staphylococcus aureus-induced arthritis causes rapid joint destruction, often leading to disabling joint damage despite Antibiotics. We have previously shown that interleukin-15 (IL-15) inhibition without Antibiotics is beneficial in S. aureus-induced arthritis. We therefore hypothesized that the inhibition of IL-15, in combination with Antibiotics, might represent a useful therapy that would reduce inflammation and joint destruction but preserve the host's ability to clear the Infection. Female wild-type C57BL/6 mice were intravenously inoculated with the toxic shock syndrome toxin 1 (TSST-1)-producing LS-1 strain of S. aureus with 0.8 × 10⁸ CFU S. aureus LS-1/mouse. Three days later, treatment consisting of cloxacillin, followed by flucloxacillin, together with either anti-IL-15 Antibodies (aIL-15ab) or control Antibodies, was started. Studied outcomes included survival, weight change, Bacterial clearance, and joint damage. 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 or weight change, or compromise the host's ability to clear the Infection. Since 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 since it reduces synovitis and bone erosions but has a limited effect on cartilage destruction.