Role of anti-inflammatory cytokine IL-35 in the effects of sublingual immunotherapy
Monday, March 5, 2018
South Hall A2 (Convention Center)
Hideaki Kouzaki, MD, Atsushi Yuta, MD, Masahiko Arikata, Takeshi Shimizu

The immunologic tolerant state following allergen immunotherapy is associated with the induction of distinct phenotypes of regulatory T-cells or B-cells. IL-35 was recently identified as an anti-inflammatory cytokine. However, IL-35 bioactivity is not fully understood in human. We investigated the role of IL-35 production in the effects of sublingual immunotherapy (SIT).


The bioactivity of human recombinant IL-35 was examined using PBMC from patients with Japanese cedar pollinosis (JCP). A prospective study was undertaken to evaluate the effects of SIT on IL-35 production from T cells and B cells.


Human recombinant IL-35 suppressed Japanese cedar pollen-induced production of IL-5, IFN-g, and IL-17, but not IL-10 from PBMC of JCP patients. Human recombinant IL-35 directly suppressed IL-5 and IL-13 production from memory CD4+ T-cells and from cocultured DCs/CD4+ T cells. The percentage of IL-35 positive CD4+ T-cells and IL-35 positive B-cells increased after one year treatment of SLIT. IL-35 protein from PBMC of JCP patients increased after SIT. Symptom medication score and serum IL-35 concentration of JCP patients in the peak season showed opposite correlation after SLIT.


IL-35 plays an important role in the suppression of Th2 type inflammation, and increased production of IL-35 from T cells and B cells after SLIT may influence effector cells in allergic rhinitis. Augmentation of constitutive IL-35 production from immune system is a potential therapeutic approach for allergic disorders.