IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans.
We examined the role of IL-12 in host resistance to Cryptococcus neoformans using a murine model of pulmonary and disseminated infection. In this model, mice were infected intratracheally with viable yeast cells. Mice untreated with IL-12 allowed an uncontrolled multiplication of yeast cells in the lung with infiltrations of few inflammatory cells, and a cryptococcal dissemination to the brain and meningitis by 3 weeks, resulting in death of all animals within 4-6 weeks. IL-12, when administered from the day of tracheal infection for 7 days, induced a marked infiltration of inflammatory cells, consisting mostly of mononuclear cells, and significantly reduced the number of viable yeast cells in the lung. The treatment suppressed brain dissemination, as shown by a marked reduction of yeast cells in the brain and prevention of meningitis. These effects resulted in a significant increase in the survival rate of infected mice. In contrast, late administration of IL-12 commencing on day 7 after instillation of yeast cells failed to protect the mice against infection with C. neoformans. In further experiments, early administration of IL-12 markedly induced interferon-gamma (IFN-gamma) mRNA in the lungs of infected mice, while no IFN-gamma mRNA was detected without this treatment. Our results indicate that IL-12 is effective when administered in the early period of pulmonary cryptococcal infection.
Kawakami
K
K
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Tohyama
M
M
Xie
Q
Q
Saito
A
A
D000818:Animals; D001483:Base Sequence; D003453:Cryptococcosis / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D005260:Female; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016919:Meningitis, Cryptococcal / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma