Blocking of TNF-α and IL-1 inhibits leukocyte infiltration at early, but not at late stage of S. aureus-induced arthritis and the concomitant cartilage destruction in rabbits

We investigated the involvement of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the pathogenesis of heat-killed S. aureus-induced arthritis. TNF-α and IL-1β peaked at 2 and 24 hr after the injection, respectively. Leukocyte infiltration within 12 hr of the inflammation was significantly inhibited (80%) by coinjection of anti-TNF-α mAb and IL-1 receptor antagonist (IL-1Ra) with S. aureus; however, leukocyte infiltration at 24 hr and thereafter was not inhibited by these agents. The loss of proteoglycan in S. aureus-induced arthritis was also unchanged either by anti-TNF-α mAb, IL-1Ra, or their combination. These results indicate that direct participation of TNF-α and IL-1 in the pathogenesis of S.aureus-induced arthritis may be limited to the early stage of inflammation and blocking of these cytokines did not result in diminishing the severity of inflammation. Thus, therapeutic approaches with the objective to suppress TNF-α and IL-1 may not be effective in the clinical treatment of gram-positive bacteria-induced arthritis.