Effect Of Heat-inactivated Cryptococcus Neoformans On Experimental Mice Meningoencephalitis

Cryptococus neofermans is an encapsulated yeast which causes cryptococcosis, characteristic of an initial pulmonary infection which can disseminate to cause a life threatening meningoencephalitis. Infections caused by the fungal pathogen Cryptococcus neoformans have been increasing steadily because of the onset of AIDS and the expanded use of immunosuppressive drugs. Thus, there is a strong motive to develop a vaccine or immunothrapy of this infection.We established an experimental model of murine of intracerebral inoculation (i.c.) infection with C. neoformans that evolves into lethal meningoencephalitis. Mice are individed into HCN-treated group and saline-treated group. The effect of HCN i.c. administration on experimental mouse cerebral cryptococosis was observed, especially on the following aspects: the survival time of mice, colony forming unit (CFU) of cryptococcus neoformans and the histopathologic changes. We found double HCN treatment subsequent local challenge with lethal doses of C. neoformans, control group have the effect of, prolonging survival time, decreased CFU of cryptococcus neofrmans in brain, and histopathologic changes could be seen massive local inflmmatory response. These findings show intracerebral inoculation of HCN results in the establishment of specific immune responses.At the same time we study the effect of intracerebral adminisration of heat-inactivated cryptococcus neoformans on IL-1β IL-2 IL-6 IFN-γand TNF-αin mice brains and spleens by RT- PCR method. We found HCN-treated group electrophoretic results of RT-PCR product of brains by IL-1βprimer and IL-6 primer were positive and by IL-2 IFN-γ and TNF-αprimers were negative. Saline-treated group electrophoretic results of RT-PCR products of brains by IL-1β IL-2 IL-6 IFN-γand TNF-α primers were negative. The electrophoreitc results of RT-PCR product of spleens by IL-1β IFN-γand TNF-α primers were positive and no substantial differences in the levels of cytokine gene transcripts between HCN- and saline- treated mice. Two groups of electrophoretic results of RT-PCR product of spleens by IL-2 and IL-6 primers were negative. These findings show the anticryptococcal mechanism of central nerve system probably involves HCN elicitaion of local cytokins IL-1β and IL-6.