ANTINEUTROPHIL MONOCLONAL-ANTIBODY THERAPY INHIBITS THE DEVELOPMENT OF ADJUVANT ARTHRITIS

The aim of this study was to determine the contribution of neutrophils to adjuvant arthritis (AA) by in vivo depletion of peripheral blood n eutrophils. Specific anti-neutrophil MoAb, RP3 (10 mg), or a control a ntibody was given twice daily on days 8-11 after injection of Mycobact erium tuberculosis in inbred male Sprague-Dawley rats. RP3 treatment i nhibited the neutrophil leukocytosis associated with AA (3.3 +/- 0.6 x 10(3)/mm(3) versus 21.2 +/- 6.9 x 10(3)/mm(3); P < 0.001). On day 12, control animals exhibited severe arthritis as assessed by articular i ndex (AI) (9.2 +/- 1.3), increase in paw volume (149.3 +/- 10.6%), and synovial fluid (SF) cell count (5.3 +/- 0.5 x 10(5)), RP3 treatment s ignificantly reduced AI (1 +/- 0.1; P < 0.001), paw volume (103.6 +/- 5.8%; P < 0.001) and SF cells (0.6 +/- 0.1 x 10(5); P < 0.001) without affecting cutaneous DTH (treated 0.6 +/- 0.1 mm change in thickness, control 0.8 +/- 0.2 mm; NS). Additional experiments demonstrated that CD4(+) cell depletion but not decomplementation inhibited AA developme nt and synovial neutrophil accumulation. Depletion of circulating neut rophils prevented joint inflammation and synovial leucocyte influx in AA, suggesting a pivotal role for neutrophils in the effector phase of AA. Inhibition of neutrophil accumulation by CD4(+) cell depletion an d not by decomplementation suggests that neutrophil accumulation in AA is T cell-dependent.