[Study of the prophylactic effect of human granulocyte-colony stimulating factor (G-CSF) on experimental pyelonephritis induced by Pseudomonas aeruginosa in diabetic mice]

Abstract

The compromised host has recently increased because of the improvement of medical diagnosis and technology. Infection in the compromised host is somewhat different from that in common patients, since this infection is caused by impairment of the host defense mechanism. And the compromised host easily suffers from opportunistic infections. This situation prompted us to study the effect of biological response modifiers (BRMs), which activate the host defense mechanism against infections in the compromised host. We used streptozotocin (STZ)-induced diabetic mice, as experimental models of the compromised host. First, we investigated the bactericidal capacity of the perineal exudating neutrophils in diabetic mice, as one of the host defense mechanism. Second, we also studied the effect of Granulocyte-Colony Stimulating Factor (G-CSF) on diabetic mice with ascending pyelonephritis by P. aeruginosa. At 1 and 2 weeks after inducing the diabetic state, no difference was found in the bactericidal capacity of the perineal exudating neutrophils between normal mice and diabetic mice. At 3 weeks, however, this bactericidal capacity was markedly suppressed in these mice. This result suggested that a depression of host defense mechanisms in diabetics was caused by, in part, a suppression of bactericidal capacity of neutrophils. When G-CSF (2 micrograms/mouse) was injected subcutaneously once a day into diabetic mice, the suppression of the bactericidal capacity of neutrophils significantly recovered. We thus studied the effect of G-CSF on diabetic mice against infection. Diabetic mice increased their susceptibility to bacterial infection more than normal mice. In diabetic mice, administration of G-CSF (2 micrograms/mouse) yielded a lower incidence of infection and infection-induced mortality than those of controls. These data show that G-CSF may be of great value for prevention and treatment of opportunistic infections in the compromised host, especially in patients whose bactericidal capacity of neutrophils is depressed, as in diabetics.