In vivo activation of neutrophil function in hamsters by recombinant human granulocyte colony-stimulating factor

Abstract

The in vivo effect of Escherichia coli-derived recombinant human granulocyte colony-stimulating factor on neutrophil function was studied in golden Syrian hamsters. Significant increases in superoxide generation and specific binding of N-formylmethionyl-leucyl-phenylalanine were observed in neutrophils isolated 4 h following a single subcutaneous injection of the factor (30 micrograms/kg). However, phagocytotic activity was not significantly stimulated in hamsters treated with the factor. Recombinant human granulocyte colony-stimulating factor hastened the recovery of peripheral neutrophil counts in animals made leukopenic by prior treatment with cyclophosphamide. Beginning several hours after infection, resistance to lethal infection following intraperitoneal injection of Staphylococcus aureus was increased when neutropenic animals were treated daily with the factor. This protective effect was associated with increased peritoneal neutrophil counts and a decreased incidence of positive peritoneal bacterial cultures at 24 h after the start of treatment. These results suggest that recombinant human granulocyte colony-stimulating factor may be a useful adjunct in the treatment of bacterial infections in neutropenic patients.

Granulocyte colony‐stimulating factor enhances protection by anti‐K1 capsular IgM antibody in murine Escherichia coli sepsis

“…Also, enhanced neutrophil recruitment and hence phagocytosis and bacterial killing may explain the lower levels of blood bacteraemia and TNF activity observed in G-CSF-treated animals. Our results confirm previous reports suggesting that G-CSFmediated protection in animal models of abdominal infection relates to enhancement of neutrophil recruitment to the site of infection [14], of neutrophil function [8,14], of bacterial killing [10], and to attenuation of the systemic TNF-induced inflammatory response [10,14].…”

“…Several recent studies have suggested a potential role for G-CSF in the management of a variety of non-neutropenic infections (reviewed in Ref. 1), including abdominal infections [8][9][10]. We have shown that G-CSF enhances the protection afforded by anti-K1 IgM MAb 58-24 in a non-neutropenic E. coli O7:K1 peritonitis model.…”

Synovial Fluid from Rheumatoid Arthritis Patients Induces Polyclonal Antibody Formation in Vivo

“…The biological activity resembles that of several other lymphokines and lack of species specificity is not unusual for such substances. As an example, human granulocytecolony-stimuiating factor has activity in hamsters [9]. hIL-I can activate mouse monocytes [29], hIL-3 works in non-human primates [lO].…”

Production of Tumor Necrosis Factor‐α in Granulocytopenic Mice with Pulmonary Candidiasis and Its Modification with Granulocyte Colony‐Stimulating Factor

“…C. albicans has been reported to cause septic shock in such granulocytopenic patients (17,31). Previously, tumor necrosis factor-a (TNF-a) was demonstrated to be a principal mediator of endotoxic shock syndrome, and mice administered with this cytokine reacted similarly to patients with endotoxemia (4,6 (10,21,22,26). In addition, our previous study (15) demonstrated that prophylactic treatment with G-CSF was effective in the protection of granulocytopenic mice from pulmonary candidiasis when used by itself or in combination with antifungal agents.…”