Effects of Granulocyte Colony Stimulating Factor and Monobactam Antibiotics (Aztreonam) on Neutrophil Functions in Sepsis

Abstract

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 μg/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 O 2 production when compared with PMNs from control animals. A single injection of rG-CSF restored both the depressed chemotaxis and the O 2 production to levels greater than those of controls. Although a single injection of Aztreonam could not improve the suppressed O 2 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.