Retention of amphotericin-B therapeutic efficacy at half doses by synergistic activation of phagocytes.
Amphotericin B (AMB) is a mainstay in the treatment of serious systemic fungal infections, such as those occurring prevalently in immuno-compromised patients treated with immunosuppressive agents or affected by Acquired Immunodeficiency Syndrome (AIDS). However AMB is an extremely toxic agent whose therapeutical utilization is often accompanied by acute side effects and chronic impairment of renal function. It is here reported that the preactivation of polymorphonucleated cells (PMN) in vivo, by a new immunomodulatory agent (PCF 39:N alpha-5[1,6,dihydro-(6-oxo-9 purinyl) pentoxycarbonyl]-L-Arginine) allows marked reduction of the AMB doses with full retention of therapeutic efficacy. This was observed in an experimental fungal infection induced in mice by intravenous inoculation of Candida albicans.
Cornaglia-Ferraris
P
P
Pediatric Oncology Research Lab, Gaslini Children's Hospital, Genova, Italy.
Rossi
E
E
Perezzani
L
L
Stradi
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000633:toxicity; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007042:Hypoxanthines / Q000494:pharmacology* / Q000627:therapeutic use; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced / Q000150:complications; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D007042:Hypoxanthines; C054420:PCF 39; D000666:Amphotericin B; D003520:Cyclophosphamide; D001120:Arginine