G-CSF immunotherapy for treatment of acute disseminated murine melioidosis
Kellie Powell1, Glen Ulett, Robert Hirst
1Department of Microbiology and Immunology, James Cook University, Townsville, Qld, Australia.
Abstract:
Burkholderia pseudomallei, the causative agent of melioidosis, is an important pathogen in tropical regions of Australia and Southeast Asia. Antibiotic therapy can be ineffective in patients with acute septicaemic melioidosis. It has been proposed that adjunctive immunotherapy using granulocyte colony stimulating factor (G-CSF) combined with antibiotics may provide an alternative approach to antibiotics alone. We have developed a murine model for melioidosis that allows novel treatment approaches to be investigated. This study looked at the potential for murine G-CSF therapy both alone and as an adjunct in the treatment of acute disseminated B. pseudomallei infection in BALB/c mice. A number of therapeutic variables involving ceftazidime and recombinant murine G-CSF were studied. Surviving mice were sacrificed and splenic bacterial loads were determined. Combining recombinant murine G-CSF with ceftazidime offered no advantage over ceftazidime alone. Pre-treatment with recombinant murine G-CSF did not demonstrate a significant benefit. This would suggest that adjunct immunotherapy using G-CSF is of limited benefit.
Insights
Granulocyte colony-stimulating factor (G-CSF) combined with antibiotics did not improve treatment for acute melioidosis in mice. Adjunctive immunotherapy with G-CSF showed limited benefit against Burkholderia pseudomallei infection.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is prevalent in tropical regions.
- Antibiotic therapy is often ineffective for acute septicaemic melioidosis.
- Granulocyte colony-stimulating factor (G-CSF) is explored as an adjunctive immunotherapy.
Purpose of the Study:
- To investigate the efficacy of murine G-CSF therapy alone and with ceftazidime.
- To evaluate G-CSF as an adjunct treatment for acute disseminated B. pseudomallei infection in a murine model.
Main Methods:
- Development of a murine model for melioidosis.
- Administration of ceftazidime and recombinant murine G-CSF in various therapeutic combinations.
- Assessment of splenic bacterial loads in surviving mice.
Main Results:
- Combining G-CSF with ceftazidime offered no significant advantage over ceftazidime alone.
- Pre-treatment with G-CSF did not yield a significant therapeutic benefit.
- Splenic bacterial loads were not significantly reduced by G-CSF adjunct therapy.
Conclusions:
- Adjunctive immunotherapy using G-CSF has limited benefit in treating acute disseminated B. pseudomallei infection.
- Current G-CSF treatment strategies are unlikely to enhance antibiotic efficacy for melioidosis.
- Further research may be needed to explore alternative immunotherapy approaches.
