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

Abstract

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.

Urolithin B alleviates Helicobacter pylori‐induced inflammation and oxidative stress in mice

“…Nevertheless, the mRNA expression of CCL2 and CXCL1 was significantly reduced in Group HP‐UB compared to Group HP. CCL2, also known as MCP‐1, is the primary chemokine responsible for attracting monocytes to inflammation sites 44–46 . Elevated expression levels of CCL2 are associated with various diseases characterized by inflammation 47,48 .…”

“…*p < 0.05; **p < 0.01; ***p < 0.001; and ns p > 0.05. primary chemokine responsible for attracting monocytes to inflammation sites. [44][45][46] Elevated expression levels of CCL2 are associated with various diseases characterized by inflammation. 47,48 As can be seen in Figure 9, the expression of CCL2 in Group HP was significantly different from that in Group HP-UB.…”

IL-15 deficiency alleviates steroid-induced osteonecrosis of the femoral head by impact osteoclasts via RANKL-RANK-OPG system

“…Our investigation not only clarifies the inhibitive effects of IL-15 deficiency on RANKL-induced osteoclast formation [31], but also indicates that IL15 inhibition can be utilized as a potential target for osteonecrosis in steroid-induced ONFH patients. But perhaps more significantly, in consideration of the contribution of IL15 in bone resorption and inflammation, IL15 inhibition will also apply to Staphylococcus aureus-induced arthritis [32], which can cause rapid joint destruction and disabling joint damage despite antibiotics utilization. All of these indicate the necessity of further detailed mechanism research about IL15 in osteonecrosis.…”