A modified recombinant human
granulocyte colony-stimulating factor (rhG-CSF),
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. Recently, the application of
G-CSF against
infectious diseases has been considered, and some animal experiments have been carried out to support its in clinical applications. Patients with underlying diseases such as
leukemia or
cancer often have
recurrent infections because of reduced number and functions of neutrophils, which mediate an early stage of host defense. We investigated the prophylactic effect of
KW-2228 against an experimental systemic
infection with Pseudomonas aeruginosa in
tumor-bearing mice (colon 26: BALB/c) treated with
cyclophosphamide.
KW-2228 (0.25-2.0 micrograms/mouse) was administered (s.c.) once a day for 4 days before the experimental
bacterial infection. As a result of
KW-2228 administration, the reduction in peripheral blood neutrophils usually caused by the injection with
cyclophosphamide was prevented markedly.
KW-2228 displayed excellent protective potency dose-dependently against the
infection with P. aeruginosa in
tumor-bearing mice. These data show the possibility that prophylactic
therapy with
KW-2228 may augment the host defense of immunocompromised patients to
infections. It present, clinical efficacy studies on
KW-2228 are under way.