Open AccessAnti‐neutrophil monoclonal antibody therapy inhibits the development of adjuvant arthritis
Author(s) -
SANTOS L. L.,
MORAND E. F.,
HUTCHINSON P.,
BOYCE N. W.,
HOLDSWORTH S. R.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1997.263-ce1154.x
Subject(s) - leukocytosis , arthritis , immunology , medicine , absolute neutrophil count , synovial fluid , monoclonal antibody , inflammation , neutrophile , antibody , pathology , toxicity , osteoarthritis , neutropenia , alternative medicine
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 × 10 3 /mm 3 versus 21.2 ± 6.9 × 10 3 /mm 3 ; 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 × 10 5 ). 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 × 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 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.