The ubiguitous fungal pathogens Cryptococcus neoformans and Candida albicans are known to be opportunists that causes serious life-threatening in both healthy and immunocompromised persons, particularly patients with AIDS as well as those with
undergoing cancer therapy. The cell-mediated immunity plays a great role in host resistance to cryptococcosis and candidiasis and cell-mediated immunity requires release of cytokines. The recent reports demonstrated that IL-4 appears important
pathogenically since IL-4 suppress the secretion and/or host defense effects of activating cytokines including IFN-γand IL-2.
In this sudy, the role of endogenous IL-4 in resistance of mice to the infection of C. neoformans and c. albicans was investigated by in vivo administration of an anti-IL-4 monoclonal antibody911B110. Mice were treated with single intraperitoneal
injection of 0.1mg of anti-IL-4 MAb 24 hr before or after intravenous inoculation of C. neoformens or C. albicans. The colony forming units(CFU) of C. neoformans in the lungs, brains, livers, spleens nd kidneys of anti-IL-4 MAb-treated and
control
mice
were enumerated at 4 or 9 days after infection. anti-IL-4 MAb treatment 24 hr before infection significantly reduced the number(CFU) of C. neoformans recovered from their lungs, brains, livers, spleens and kidneys at 4 days after infection
compared
with
that of control mice Anti-IL-4 MAb also simlarly reduced the number of C. neoformans recovered from various clgans(except brain ) 9 dyas after infectiol. The administration of anti-IL-4 MAb decreased the number of CFU of C. neoformans recovered
from
lungs, livers and spleens only when administered before infection. However, the number of C. neoformans Recovered from brains and kindneys were decreased when anti-IL-4 MAb were administered 24 hr before or after infection, suggesting brain and
kidney
may be more sensitive than spleen and liver to the effects of endogenous IL-4. Additional multiple injections of anti-IL-4 MAb before or after infection did not further enhance the resistance to infections to C. neoformans or C. albicans. A
single
anti-LIL-4 MAb administration 24 hr before infection reduced the number of C. neoformans recovered from spleens by 3 weeks after infection, but not by 4 weeks. Furthermore, anti-IL-4 MAb administration enhanced survival of mice that had been
experimentally infected with C. neoformans compared with control mice. The effects of anti-IL-4 MAb on delayed-type hypersensitivity (DTH0 reaction to cryptococcal culture filtrate(CneF) antigen was also investigated and it was found that a
single
administration of anti-IL-4 MAb 24 hr before immunization did not change the DTH reaction to CneF. Anti-IL-4 MAb administration, signgle or multiple, before infection also caused the reduction of the CFU of C. albicans recovered from kindneys.
Taken
together, these results provide an evidence that anti-IL-4 MAb administration may increase the resistance to infections with C. neoformans or C. albicans, suggesting that endogrnous IL-4 has a deleterious effect on host defence against the
infectons.
This work also indicates that anti-IL-4 may be important adjuncts in the treatment of cryptococcosis and candidiasis and deserve further study.
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