CYTOKINE AND NITRIC-OXIDE PRODUCTION IN THE ACUTE-PHASE OF BACTERIAL-CELL WALL-INDUCED ARTHRITIS

We have investigated the temporal relationship among proinflammatory c ytokine expression, nitric oxide (NO) production and joint inflammatio n in the acute phase of bacterial cell wall-derived peptidoglycan poly saccharide(PG/PS)-induced arthritis. Acute joint inflammation was indu ced in female LEW/N rats by a single intraperitoneal injection of PG/P S. Arthritis index and paw volume were quantified and joint histopatho logy was evaluated during acute joint inflammation (0-10 days). Tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) w ere determined by bioassay whereas nitric oxide (NO) was quantified by measuring serum nitrate/nitrite levels via the Griess procedure. We f ound that serum levels of TNF and serum IL-1 preceded the increase in IL-6 and NO production. Furthermore, the production of these proinflam matory cytokines and NO preceded bone erosion and osteoclast activity. Erosion of subchondral bone preceded pannus formation and cellular sy novitis in the acute phase of PG/PS-induced arthritis. The temporal ex pression of TNF, IL-1, IL-6 and NO suggest a cascade of inflammatory m ediators in which monocytes and macrophages respond to PG/PS with enha nced synthesis of TNF and IL-1, which may in turn promote the synthesi s of IL-6 and NO. We postulate that one or more of these inflammatory events are responsible for initiating the subchondral bone erosion obs erved in acute joint inflammation.