Lentinan ameliorates burn sepsis by attenuating CD4 CD25 Tregs.

Aim: The aim of our study was to investigate the effect of lentinan on regulatory T cells (Tregs) in sepsis, especially on the generation of interleukin (IL)-10 via regulation of Erk-FoxO1 signaling.

Methods: BalB/c mice were randomized into five groups: sham group, the group with burns plus Pseudomonas aeruginosa infection, and the groups with burns plus P. aeruginosa infection administered 40, 100, and 250mg/kg of lentinan. The mice were sacrificed on postburn days 0, 1, 2, 3, and 4, respectively, with eight animals per group at each time point. The peripheral blood CD4 CD25 Tregs and CD4 T cells were isolated using magnetic microbeads. The phenotypes were analyzed by flow cytometry. The cytokine levels were determined with enzyme-linked immunosorbent assay (ELISA). Signal transduction was studied by Western blot, quantitative polymerase chain reaction (qPCR), and luciferase assay.

Results: The IL-10-producing capacity of CD4 CD25 Tregs was significantly enhanced in the group with burns plus P. aeruginosa infection, compared with the sham group. Administration of lentinan significantly decreased IL-10 production and FoxP3 expression of CD4 CD25 Tregs. The proliferative activities of CD4 T cells, however, were restored. Lentinan decreased lipopolysaccharide (LPS)-induced IL-10 production in the Tregs isolated from burned mice. In addition, lentinan attenuated LPS-stimulated Erk-FoxO1 activation.

Conclusions: Lentinan may improve the outcome of postburn sepsis by suppressing LPS-triggered Erk-FoxO1 activation. Consequently, the hyperfunction of CD4 CD25 Tregs is inhibited, leading to a shift in the inflammatory status from Th2 to Th1 in postburn sepsis.