title: Anti-neutrophil monoclonal antibody therapy inhibits the development of adjuvant arthritis.
abstract: 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 x 10(3)/mm3 versus 21.2 +/- 6.9 x 10(3)/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 x 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 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 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.
authors.affiliation: Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Australia.
authors.forename: L L
authors.initials: LL
authors.lastname: Santos
authors.forename: E F
authors.initials: EF
authors.lastname: Morand
authors.forename: P
authors.initials: P
authors.lastname: Hutchinson
authors.forename: N W
authors.initials: NW
authors.lastname: Boyce
authors.forename: S R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000517:prevention & control*; D006968:Hypersensitivity, Delayed / Q000628:therapy; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal