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[Study of the prophylactic effect of ubenimex on experimental pyelonephritis induced by Pseudomonas in neutropenic
Abstract:
We investigated the prophylactic effect of Ubenimex on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group). This experimental model was established by a two course administration of cyclophosphamide, so that it kept the mice in a neutropenic status (around 2000 white blood cells/mm3) from the time of infection to the time of sacrifice. The cyclophosphamide-treated group increased their susceptibility more than the control group. In the cyclophosphamide-treated group, the prophylactic administration of Ubenimex (100 micrograms/day/mouse) did not produce significant decreases of infection-induced mortality rate, but yielded a lower incidence of infection than of saline alone. Administration of Ubenimex was not able to increase the number of neutrophils during the experiment. An investigation of the bactericidal capacity of peritoneal exudating neutrophils revealed that Ubenimex prophylactic administration accelerated its capacity, although cyclophosphamide alone did not. These results suggest that Ubenimex has a prophylactic effect on bacterial infection in neutropenic mice, and that this effect, in part, depends upon the acceleration of bactericidal capacity of neutrophils produced by Ubenimex.
Insights
Ubenimex shows a prophylactic effect against Pseudomonas aeruginosa infection in neutropenic mice by enhancing neutrophil bactericidal capacity, despite not increasing neutrophil count. This suggests Ubenimex aids in combating bacterial infections in immunocompromised individuals.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Neutropenia increases susceptibility to bacterial infections, particularly Pseudomonas aeruginosa.
- Ascending pyelonephritis is a severe condition often exacerbated by neutropenia.
- Cyclophosphamide is used to induce a neutropenic state in experimental models.
Purpose of the Study:
- To investigate the prophylactic efficacy of Ubenimex in a mouse model of Pseudomonas aeruginosa-induced pyelonephritis.
- To determine if Ubenimex influences neutrophil counts or function in neutropenic mice.
- To elucidate the mechanism of Ubenimex's potential protective effect.
Main Methods:
- Establishment of an ascending pyelonephritis model in mice using Pseudomonas aeruginosa and cyclophosphamide-induced neutropenia.
- Prophylactic administration of Ubenimex (100 µg/day/mouse) or saline.
- Monitoring of infection-induced mortality and incidence.
- Assessment of neutrophil counts and ex vivo bactericidal capacity of neutrophils.
Main Results:
- Ubenimex did not significantly reduce mortality but lowered infection incidence in neutropenic mice.
- Ubenimex administration did not increase neutrophil numbers.
- Prophylactic Ubenimex significantly accelerated the bactericidal capacity of peritoneal neutrophils.
Conclusions:
- Ubenimex exhibits a prophylactic effect against bacterial infection in neutropenic mice.
- This protective effect is partly attributed to Ubenimex's ability to enhance neutrophil bactericidal function.
- Ubenimex may be a potential therapeutic agent for bacterial infections in immunocompromised patients.