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 immunocompr omized patients. Granulocyte colony-stimulating factor (G-CSF) reduces mort ality in experimental invasive candidiasis, Covalent conjugation of polyeth ylene-glycol (peg) to proteins increases their stability and in vivo bioact ivity, 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 c hronic candidiasis models in non-neutropenic FVB/N mice. Peg-G-CSF rapidly increased circulating polymorphonuclear leukocyte (PMNL) numbers in mice, s ustaining high for >4 days. Candida albicans outgrowth from kidneys of infe cted mice was strongly reduced after peg-G-CSF treatment (5.76 log cfu/g ki dney vs 7.66 control), with absence of hyphal outgrowth and enhanced PMNL i nflux. Moreover, peg-G-CSF increased survival of C, albicans-infected mice, whereas efficacy of uncoupled G-CSF was obtained only after repeated treat ment, These data document a potent in vivo biological effect of peg-G-CSF, resulting in strongly enhanced resistance against systemic candidiasis, (C) 2000 Academic Press.