Paeoniflorin augments systemic Candida albicans infection through inhibiting Th1 and Th17 cell expression in a mouse model

Paeonifiorin (PF), a Chinese herbal medicine, has been widely used in clinical practice in China because of its dual immunoregulatory effects. A previous study found that PF inhibited the biofihn formation of Candida albicans (C. albicans) in vitro; however, whether PF plays an antifungal role in vivo is still unexplored. In this study, we sought to examine the effect of PF alone or in combination with an antifungal agent, fluconazole (FCZ), using a mouse model of systemic candidiasis. The results showed that the survival time of mice treated with PF alone or PF + FCZ decreased compared with the Infected alone and FCZ treated groups, respectively (8.20 +/- 1.75 vs 10.40 +/- 2.50 days, P < 0.05; 24.60 +/- 6.55 vs 29.00 +/- 3.16 days, P < 0.05). The fungal burden in the kidney of mice increased in the PF alone and PF + FCZ treated groups compared with the Infected alone or FCZ treated group. Furthermore, it was found that the PF and PF + FCZ treated groups showed significantly decreased levels of serum interferon gamma (IFN-gamma), interleukin (IL)-17, and IL-22, and an increased level of serum IL-4; PF had no effect on the production of tumor necrosis factor alpha (TNF-alpha). PF alone or in combination with FCZ decreased the proliferation of Thl (IFN-gamma(+) CD4(+)) and Th17 cells (IL-17(+) CD4(+)) and increased the expression of Th2 cells (IL-4(+) CD4(+)). These results suggested that PF treatment could be detrimental to the host response to systemic C. albicans infection in mice. Thus, caution might be required for clinical use of PF in patients with fungal infection.