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Keywords:

  • neutrophil;
  • adjuvant arthritis;
  • CD4+ cell;
  • monoclonal antibody;
  • complement

The aim of this study was to determine the contribution of neutrophils to adjuvant arthritis (AA) by in vivo depletion of peripheral blood neutrophils. Specific anti-neutrophil MoAb, RP3 (10 mg), or a control antibody was given twice daily on days 8–11 after injection of Mycobacterium tuberculosis in inbred male Sprague-Dawley rats. RP3 treatment inhibited the neutrophil leukocytosis associated with AA (3.3 ± 0.6 × 103/mm3versus 21.2 ± 6.9 × 103/mm3; P < 0.001). On day 12, control animals exhibited severe arthritis as assessed by articular index (AI) (9.2 ± 1.3), increase in paw volume (149.3 ± 10.6%), and synovial fluid (SF) cell count (5.3 ± 0.5 × 105). RP3 treatment significantly reduced AI (1 ± 0.1; P < 0.001), paw volume (103.6 ± 5.8%; P < 0.001) and SF cells (0.6 ± 0.1 × 105; 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 development and synovial neutrophil accumulation. Depletion of circulating neutrophils 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 and not by decomplementation suggests that neutrophil accumulation in AA is T cell-dependent.