Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice.
A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.
D000380:Agranulocytosis / Q000188:drug therapy*; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy*; D002177:Candidiasis / Q000188:drug therapy*; D003115:Colony-Stimulating Factors / Q000302:isolation & purification / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy; D016179:Granulocyte Colony-Stimulating Factor; D007958:Leukocyte Count / Q000187:drug effects; D008163:Luminescent Measurements; D051379:Mice; D009503:Neutropenia / Q000188:drug therapy*; D009504:Neutrophils / Q000502:physiology; D010529:Peritoneal Cavity / Q000166:cytology; D011552:Pseudomonas Infections / Q000188:drug therapy; D012706:Serratia marcescens; D013203:Staphylococcal Infections / Q000188:drug therapy
D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor