Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1→3)-β-Glucans from Fungi

Abstract

The immunomodulating effects of various gel-forming (1→3)-β-glucans, grifolan (GRN), SSG, sonifilan (SPG) and alkaline-treated SPG (SPG-OH), on balancing helper T cell activity were examined in a murine model. Plasma from mice that were injected with GRN or SPG-OH and trinitrophenyl ovalbumin (TNP-OVA) contained TNP-specific antibodies of both IgG1 and IgG2a isotypes. Administration of SSG and TNP-OVA significantly augmented the synthesis of IgG2a antibodies, while the synthesis of IgG1 was reduced. However, SPG did not enhance the antibody response. In the culture supernatants of splenocytes obtained from GRN- or SPG-OH-administered mice, high levels of IgG1 and low levels of IgG2a and IFN γ were detected. In contrast, high levels of IgG2a and IFN γ and low levels of IgG1 were detected in the case of administration of SSG. Furthermore, it was shown by intracellular cytokine staining that the proportion of IFN γ⁺CD4⁺ double-positive cells among the CD4⁺ cells from mice administered SSG was most strongly increased by addition of PMA and A23187. On the other hand, the expression of IL-12 p40 mRNA was more markedly elevated in splenocytes after combined administration of TNP-OVA plus SSG than after administration of TNP-OVA alone. The highest IFN γ production was observed when adherent cells of mice administered TNP-OVA and SSG were cultured with TNP-primed lymphocytes. This effect of administration of SSG on IFN-γ production was completely inhibited by addition of anti-IL-12 mAb. In conclusion, our study showed that β-glucans have various effects on the Th1 or Th2-dependent antibody subclasses, in particular. SSG induces the development of Th1 cells via the IL-12 pathway.