Granulocyte colony stimulating factor therapy of experimental cryptococcal meningitis.
Cryptococcal meningitis was induced in mice using intracerebral injection of Cryptococcus neoformans. Beginning either 3 days before or 1 day after infection, mice were treated with human recombinant granulocyte colony stimulating factor (hGCSF). In high doses hGCSF reduced the brain tissue burden of C. neoformans but had no effect on survival. The effect of hGCSF was dependent on size of the infecting dose and time of administration. A large innocula of C. neoformans, or when hGCSF was initiated after infection, there was no added benefit. Some groups of mice also received low doses of fluconazole beginning 1 day after infection. Fluconazole both prolonged survival and reduced brain tissue counts of C. neoformans. Combined cytokine/fluconazole therapy was superior to either agent given alone. These studies suggest that hGCSF can add to the efficacy of fluconazole therapy in murine cryptococcosis, and suggest that polymorphonuclear leucocytes contribute to host defence in cryptococcal meningitis. The relative potency of fluconazole appears greater than hGCSF.
Graybill
J R
JR
Department of Medicine, University of Texas Health Science Center at San Antonio, USA.
Bocanegra
R
R
Lambros
C
C
Luther
M F
MF
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D001921:Brain / Q000382:microbiology / Q000473:pathology; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000302:isolation & purification; D015725:Fluconazole / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D016919:Meningitis, Cryptococcal / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins / Q000627:therapeutic use
D000935:Antifungal Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015725:Fluconazole