Effects of granulocyte colony stimulating factor in a nonneutropenic rodent model of Escherichia coli peritonitis

Despite improved antimicrobials and advances in caring for critically ill patients, mortality from sepsis is still unacceptably high. Upregulation of the cellular immune system is one strategy for decreasing mortality in subjects with severe sepsis, which appears to be promising. Granulocyte colony stimulating factor (G-CSF) has been used successfully to decrease mortality in neutropenic subjects with sepsis. In this study, we have investigated whether pretreatment with G-CSF decreases mortality in non- neutropenic rodents with lethal Escherichia call peritonitis. We implanted agar pellets impregnated with 5 x 10⁸ cfu of Escherichia coli into the peritoneal cavities of rats pretreated with 50 μg/kg of G-CSF or an equal volume of 5% dextrose in water (D5W). Survival of these animals increased from 38 to 78% with G-CSF pretreatment. We also demonstrated an 11-fold increase in the number of polymorphonuclear leukocytes (PMNs) in animals treated with G-CSF. This increase in cells was seen initially only in the peripheral circulation. Twenty-four hours after induction of peritonitis, however, there was a threefold greater increase in number of PMNs recovered from the peritoneal cavities of animals pretreated with G-CSF as compared to those treated with D5W. PMNs recovered from the peritoneal cavities of these animals had significantly elevated bactericidal activity (74% killing vs 53% killing) as compared to those cells recovered from the peritoneal cavities of control animals. These results indicate that G-CSF pretreatment improves survival of non-neutropenic animals with lethal Escherichia call peritonitis by enhancing the cellular arm of the immune response.