In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3
-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1
cell line to produce the superoxide anion, increasing
in vitro microbicidal activity, suggesting that this drug can be
used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated
the potential of the in vivo administration of BAY 41-2272 for the treatment of
Candida albicans
and
Staphylococcus
aureus
infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal
treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to
macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate
acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing
the death rate due to intraperitoneal inoculation of
C. albicans, but not
S. aureus. However, we found that
in vitro
stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both
pathogens. Our results show that the prevention of death by the treatment of
C. albicans-infected mice with BAY 41-
2272 might occur primarily by the modulation of the host immune response through macrophage activation.
