TREATMENT WITH RECOMBINANT GRANULOCYTE-COLONY-STIMULATING FACTOR (FILGRASTIN(TM)) STIMULATES NEUTROPHILS AND TISSUE MACROPHAGES AND INDUCESAN EFFECTIVE NONSPECIFIC 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 , Eve determined the effect of granulocyte colony-stimulating factor ( G-CSF) on the outcome of MAC infection in mice. C57BL/6 bg(+)/bg(-) bl ack mice were intravenously infected with 1x10(7) MAC and then divided into four experimental groups to receive G-CSF as follows: (i) 10 mu g/kg/day; (ii) 50 mu g/kg/day; (iii) 100 mu g/kg/day; (iv) placebo con trol. 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 an d 50 mu g/kg/day doses significantly decreased the number of viable ba cteria in liver and spleen after 2 weeks (approximate to 70.5% and 69. 0%, respectively), and after 4 weeks (approximate to 53% and 52%, resp ectively, P<0.05 compared with placebo control), Treatment with 100 mu g/kg/day did not result in decrease of bacterial colony-forming units in the liver and spleen after 4 weeks. Administration of G-CSF induce d interleukin-10 (IL-10) and IL-12 production by splenocytes. To exami ne if the protective effect of G-CSF was accompanied by the activation of phagocytic cells, blood neutrophils and splenic macrophages were p urified from mice receiving G-CSF and their ability to kill MAC was ex amined ex vivo. Neutrophils and macrophages from G-CSF-treated mice we re able to inhibit the growth of or to kill MAC ex vivo, while phagocy tic cells from untreated control mice had no anti-MAC effect. These re sults suggest that activation of neutrophils appears to induce an effe ctive non-specific host defence against MAC, and further studies shoul d aim for better understanding of the mechanisms of protection.