Treatment with recombinant granulocyte colony-stimulating factor (Filgrastin) stimulates neutrophils and tissue macrophages and induces an effective non-specific response against Mycobacterium avium in mice.
A role of neutrophils in the host response against Mycobacterium avium (MAC) has recently been suggested. To investigate this matter further, we determined the effect of granulocyte colony-stimulating factor (G-CSF) on the outcome of MAC infection in mice. C57BL/6bg+/bg- black mice were intravenously infected with 1 x 10(7) MAC and then divided into four experimental groups to receive G-CSF as follows: (i) 10 micrograms/kg/day; (ii) 50 micrograms/kg/day; (iii) 100 micrograms/kg/day; (iv) placebo control. Mice were killed at 2 and 4 weeks of treatment to determine the bacterial load of liver and spleen. Treatment with G-CSF at both 10 and 50 micrograms/kg/day doses significantly decreased the number of viable bacteria in liver and spleen after 2 weeks (approximately 70.5% and 69.0%, respectively), and after 4 weeks (approximately 53% and 52%, respectively, P < 0.05 compared with placebo control). Treatment with 100 micrograms/kg/day did not result in decrease of bacterial colony-forming units in the liver and spleen after 4 weeks. Administration of G-CSF induced interleukin-10 (IL-10) and IL-12 production by splenocytes. To examine if the protective effect of G-CSF was accompanied by the activation of phagocytic cells, blood neutrophils and splenic macrophages were purified from mice receiving G-CSF and their ability to kill MAC was examined ex vivo. Neutrophils and macrophages from G-CSF-treated mice were able to inhibit the growth of or to kill MAC ex vivo, while phagocytic cells from untreated control mice had no anti-MAC effect. These results suggest that activation of neutrophils appears to induce an effective non-specific host defence against MAC, and further studies should aim for better understanding of the mechanisms of protection.
Bermudez
L E
LE
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, USA.
Petrofsky
M
M
Stevens
P
P
D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008099:Liver / Q000382:microbiology; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium; D018375:Neutrophil Activation; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*
D011994:Recombinant Proteins; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D000069585:Filgrastim