BLOCKING OF TNF-ALPHA 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-alpha (TNF-al pha) and interleukin-1 beta (IL-1 beta) in the pathogenesis of heat-ki lled S. aureus-induced arthritis. TNF-alpha and IL-1 beta peaked at 2 and 24 hr after the injection, respectively, Leukocyte infiltration wi thin 12 hr of the inflammation was significantly inhibited (80%) by co injection of anti-TNF-alpha mAb and IL-1 receptor antagonist (IL-1Ra) with S. aureus; however, leukocyte infiltration at 24 hr and thereafte r was not inhibited by these agents. The loss of proteoglycan in S. au reus-induced arthritis was also unchanged either by anti-TNF-alpha mAb , IL-1Ra, or their combination. These results indicate that direct par ticipation of TNF-alpha and IL-1 in the pathogenesis of S. aureus-indu ced arthritis may be limited to the early stage of inflammation and bl ocking of these cytokines did not result in diminishing the severity o f inflammation. Thus, therapeutic approaches with the objective to sup press TNF-alpha and IL-1 may not be effective in the clinical treatmen t of gram-positive bacteria-induced arthritis. (C) 1997 Academic Press , Inc.