INTERLEUKIN-4 AND INTERLEUKIN-10 EXACERBATE CANDIDIASIS IN MICE

Neutralization of endogenous interleukin (IL)-4 or IL-10 in mice with Candida albicans infection initiates or accelerates development of a T helper (Th)1-associated protective response. Here, we report the effe ct of IL-4 and IL-10 administration on the course of systemic or gastr ointestinal (GI) candidiasis and on the development of Th immunity usi ng yeast/host combinations that result either in Th1-associated self-l imiting infection (healer mice) or in Th2-associated progressive disea se (nonhealer mice). Treatment with IL-4 or IL-10 greatly exacerbated the course of systemic infection in nonhealer mice and rendered healer mice, inoculated with attenuated yeast cells, susceptible to infectio n. Under the latter conditions of yeast challenge and IL-4/IL-10 admin istration, the development of a fatal disease was associated with inhi bition of IL-12 production and detection of progressive Th2 cell domin ance. In contrast, in healer mice allowed to resolve their infections and to develop long-lived anti-candidal resistance, the expression of this acquired resistance was not impaired by IL-4 and/or IL-10, as sho wn by the outcome of reinfection with virulent yeast cells. In the GI model of infection, both IL-4 and IL-10 were found to exacerbate the c ourse of infection and to induce the appearance of CD4(+) T cells prod ucing high levels of IL-4 and IL-10 in Peyer's patches. These findings demonstrate that exogenous IL-4 and IL-10 may greatly affect the deve lopment of Th responses to C. albicans irt vivo, but do not modify the expression of established and predominant Th1 cell reactivity.