Etoposide-mediated depletion of peripheral blood monocytes post s.aureus infection attenuates septic arthritis by modulating macrophage-derived factors responsible for inflammatory destruction

Abstract

S.aureus induced septic arthritis remains a serious medical concern due to its rapidly progressive disease profile. The multidrug resistant nature of S.aureus demands the development of new strategies for the treatment of S.aureus arthritis. Since monocyte/macrophage population has been recognized as an important axis in joint inflammation and destruction, selective depletion of peripheral blood monocytes might influence the outcome and progression of the disease. Therefore, in this study we have put forward the concept of monocyte depletion by using etoposide, a drug that selectively depletes the monocyte/macrophage population. Mice were inoculated with live S.aureus for the development of septic arthritis. Post S.aureus infection, etoposide was subcutaneously injected. The severity of arthritis was found to be significantly low in the etoposide treated mice throughout the course. Arthritis index, histopathological analysis and TRAP staining images confirmed effectiveness of etoposide treatment in regulating inflammation and bone cartilage destruction. Lower levels of inflammatory cytokines, ROS, MMP-2, RANKL, OPN and plasmin reflected less severe arthritic destruction after etoposide treatment in arthritic mice. The bacterial load was not increased after etoposide treatment. Together, the presented data suggested that monocyte depletion by etoposide might represent an alternative therapeutic strategy for the treatment of S.aureus arthritis.

Keywords: Etoposide; Monocyte depletion; S.aureus; Septic arthritis.