Adjuvant effect of CpG-oligodeoxynucleotide in anti-fungal chemotherapy against fatal infection with Cryptococcus neoformans in mice.
Cryptococcal meningoencephalitis is a life-threatening infectious disease in immunocompromised patients. Unmethylated CpG-oligodeoxynucleotides (CpG-ODN) protects hosts in a mouse model. In the present study, we tested the adjuvant effect of CpG-ODN in anti-fungal chemotherapy. Administration of either fluconazole (FLCZ) or CpG-ODN was effective in extending survival, accelerating clearance of fungi and preventing disseminated infection. Combination of both agents provided more beneficial effect than either agent alone. Cytokine balance in the infected lungs was biased to Th1-type response by CpGODN, while FLCZ did not further promote. These results suggest that CpG-ODN is a promising adjuvant in chemotherapy against this infection.
Kinjo
Takeshi
T
Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Miyagi
Kazuya
K
Nakamura
Kiwamu
K
Higa
Futoshi
F
Gang
Xiao
X
Miyazato
Akiko
A
Kaku
Mitsuo
M
Fujita
Jiro
J
Kawakami
Kazuyoshi
K
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000382:microbiology; D003131:Combined Modality Therapy; D003453:Cryptococcosis / Q000188:drug therapy* / Q000276:immunology; D003455:Cryptococcus neoformans / Q000254:growth & development*; D016207:Cytokines / Q000276:immunology; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D023421:Models, Animal; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology
D000277:Adjuvants, Pharmaceutic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D015725:Fluconazole