The Arthus reaction in rodents: Species-specific requirement of complement

We induced reverse passive Arthus (RPA) reactions in the skin of rodents an d found that the contribution of complement to immune complex-mediated infl ammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiat ion of an RPA reaction, serum alternative pathway hemolytic titers decrease d significantly below basal levels, whereas classical pathway titers were u nchanged. Thus the dermal reaction proceeds coincident with systemic activa tion of complement. The serine protease inhibitor BCX 1470, which blocks th e esterolytic and hemolytic activities of the complement enzymes Cls and fa ctor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of m ajor importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases whe re complement activation is known to be detrimental.