Effects of KW-2228 on the function of polymorphonuclear neutrophils in rats for the phagocytosis and killing activity and the production of active oxygen

Abstract

KW-2228 is a novel derivative of a recombinant human granulocyte colony-stimulating factor (rhG-CSF) with a modification. KW-2228 has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. In the present study, we investigated the effect of KW-2228 on phagocytic capacity and killing action of polymorphonuclear neutrophils (PMNs) obtained from normal rats which had been treated with KW-2228 using various microorganisms, such as Candida albicans, Escherichia coli and Pseudomonas aeruginosa. We also investigated the effect of KW-2228 on the production of superoxide anion using a luminol-chemiluminescence method. KW-2228 enhanced the phagocytosis and killing activity of PMNs of rats against C. albicans and E. coli. PMNs treated with KW-2228 showed some bactericidal activity against P. aeruginosa. These data obtained with PMNs treated with KW-2228 show a correlation between the bacterial susceptibility to phagocytosis and killing action and the lunimol-dependent chemiluminescence response. These results suggest the significance and the efficacy of KW-2228 used in an additional therapy to that of antibiotics in the treatment of infections diseases. KW-2228 is currently in Phase III clinical trials in Japan.