A single injection of polyethylene-glycol granulocyte colony-stimulating factor strongly prolongs survival of mice with systemic candidiasis.
Systemic candidiasis is a life-threatening disease occurring in immunocompromized patients. Granulocyte colony-stimulating factor (G-CSF) reduces mortality in experimental invasive candidiasis. Covalent conjugation of polyethylene-glycol (peg) to proteins increases their stability and in vivo bioactivity. In this study, the effect of a single subcutaneous injection of peg-G-CSF on lethal candidiasis was assessed. This was performed in acute and chronic candidiasis models in non-neutropenic FVB/N mice. Peg-G-CSF rapidly increased circulating polymorphonuclear leukocyte (PMNL) numbers in mice, sustaining high for >4 days. Candida albicans outgrowth from kidneys of infected mice was strongly reduced after peg-G-CSF treatment (5.76 log cfu/g kidney vs 7.66 control), with absence of hyphal outgrowth and enhanced PMNL influx. Moreover, peg-G-CSF increased survival of C. albicans -infected mice, whereas efficacy of uncoupled G-CSF was obtained only after repeated treatment. These data document a potent in vivo biological effect of peg-G-CSF, resulting in strongly enhanced resistance against systemic candidiasis.
van Spriel
A B
AB
Department of Immunology, University Medical Center, Utrecht, The Netherlands.
van den Herik-Oudijk
I E
IE
van de Winkel
J G
JG
D000818:Animals; D002176:Candida albicans; D002177:Candidiasis / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins; D015996:Survival Rate
D004337:Drug Carriers; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols