Simultaneous intraperitoneal administration of OK-432 and serum enhances superoxide generation from migrated polymorphonuclear leukocytes, with special emphasis on the role of complements.

Superoxide and its derived active oxygen species are responsible for the polymorphonuclear leukocyte (PMN)-mediated tumoricidal activity which is typically shown in the intraperitoneal administration of OK-432, a biological response modifier, for cancer ascites. We examined the effects of intraperitoneal administration of OK-432 with or without syngeneic serum on superoxide generation from PMNs which migrated in the peritoneal cavity using the new method of Cypridina luciferin analog-dependent chemiluminescence for the detection of superoxide. PMNs harvested from rat peritoneal cavity 6 h after the intraperitoneal administration of OK-432 (0.25KE/kg, or 2.5KE/kg) generated larger amounts of superoxide than those harvested after intraperitoneal injection of oyster glycogen (75mg/kg) when stimulated by opsonized zymosan or phorbol myristate acetate. Simultaneous intraperitoneal administration of OK-432 and syngeneic serum induced a greater increase in PMN superoxide generation than OK-432 alone, which was reversed by a complement activation inhibitor (MX-1). Simultaneous injection of OK-432 and heat-inactivated syngeneic serum did not exhibit a significant increase in PMN superoxide generation as compared with OK-432 alone. These results provide pharmacological evidence to the satisfactory therapeutic effects of the intraperitoneal administration of OK-432 with or without serum for patients with cancer ascites, and indicate that complements, in particular C5a, are involved in this enhanced PMN-derived superoxide generation induced by the simultaneous injection of OK-432 and serum.