CYTOKINE RESPONSE TO INACTIVATED CANDIDA-ALBICANS IN MICE

Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effecters in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEG) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-Bd a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased, IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed, IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of T(H)1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement in the development of T(H)1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells. (C) 1995 Academic Press, Inc.