Differential effects of Rhodiola rosea on regulatory T cell differentiation and interferon‑γ production in vitro and in vivo.

Rhodiola rosea (R. rosea), a type of adaptogen, has been previously reported to exhibit immunostimulating activity in rodents and in human peripheral blood mononuclear cells (PBMCs) in vitro. To examine the effect of R. rosea on T cells under simulated microgravity, spaceflight analogs of human head‑down bed rest (HDBR) at ‑6˚ and murine hind limb unloading (HU) were used. A decrease in the levels of interferon‑γ (IFN‑γ) and interleukin‑17 (IL‑17) and an increase in regulatory T (Treg) cells were observed in the placebo group following HDBR. The R. rosea treated HBDR group demonstrated further decreased IFN‑γ production, however, R. rosea exhibited no effect on the ratio of circulating Tregs or Treg cell differentiation. By contrast, the treatment of R. rosea on human T cells in vitro did not alter IFN‑γ secretion, however, Treg differentiation was significantly reduced. An R. rosea‑induced upregulation of hypoxia‑inducible factor 1α (HIF‑1α) contributed to the suppression of Treg differentiation in vitro. Differences in the effect of R. rosea in vitro and in vivo were also observed using a mouse model of microgravity. The results of the current study suggest that R. rosea has differential modulatory effects on T cells in vivo and in vitro and care should be taken when evaluating the effects of R. rosea on the immune system.