Possible clinical use of a recombinant human
granulocyte colony stimulating factor (rG-CSF) and a newly developed
monobactam antibiotics (
Aztreonam) for the treatment of gram-negative
sepsis was investigated. Gram-negative
sepsis was induced in male WKA rats by cecal
ligation and
puncture (CLP). Untreated CLP rats all died by
septicemia with severe peripheral blood
leukocytopenia within 5 days after the operation. When we administered 2.0 micrograms/kg of rG-CSF and/or 20 mg/kg of
Aztreonam intravenously just after the operation, the rats survived longer than the untreated CLP rats. These drugs were found to be more effective when used in combination. Since these rats showed an increase in leukocyte counts, we next examined the changes in the functions of polymorphonuclear leukocytes (PMNs, mainly neutrophils) after the treatment. PMNs from untreated CLP rats at 24 hr after the operation exhibited enhanced
plastic-dish adherence, suppressed chemotaxis, and depressed O2 production when compared with PMNs from control animals. A single injection of rG-CSF restored both the depressed chemotaxis and the O2 production to levels greater than those of controls. Although a single injection of
Aztreonam could not improve the suppressed O2 production, it could restore the depressed chemotaxis. Interestingly, simultaneous injection of
Aztreonam with rG-CSF significantly enhanced the effect of rG-CSF on the PMN functions. These data suggest that the
Aztreonam and rG-CSF may be useful for the treatment of gram-negative
sepsis, especially when used in combination.