Impact of interleukin-32α on T helper cell-related cytokines, transcription factors, and proliferation in patients with type 2 diabetes mellitus

Objective The ability of interleukin (IL)-32 alpha to induce T helper (Th) 1, Th17, and Treg cytokines (interferon gamma [IFN-gamma], IL-17, and IL-10, respectively), and transcription factors ([signal transducer and activator of transcription (STAT) 1 and T-box (T-bet) for Th1, STAT3 and retinoid-related orphan receptor (ROR)-gamma t for Th17, and STAT5 and forkhead box P3 (Foxp3) for Treg]) were investigated in type 2 diabetes mellitus (T2DM). IL-32 alpha effects on Th cell proliferation and related factors including IL-2 and NF-kappa B were also explored. Methods Serum levels of IL-32 alpha in 31 patients and 31 healthy controls (HCs) were determined by ELISA assay. CD4(+) T cells cultured with polyclonal activators in the presence and absence of recombinant IL-32 alpha (rIL-32 alpha). Gene expressions in cultured Th cells were assessed with real-time PCR. Cytokines in supernatants were measured with ELISA. Proliferation experiments were assessed by flow cytometry. Results The patients showed significant increase in IL-32 alpha levels compared with HCs and its levels were positively correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). rIL-32 alpha enhanced IL-17 and IL-2 production, increased ROR-gamma t and NF-kappa B expression, and enhanced Th proliferation in both patients and HCs. In patients, IL-17, ROR-gamma t, NF-kappa B, and proliferation levels were higher than those in HCs, in cultures with and without rIL-32 alpha (rIL-32 alpha(+) and rIL-32 alpha(-)). IL-2 levels in rIL-32 alpha(+)cultures of patients were significantly higher than the HCs, and it was positively correlated with proliferation rate and NF-kappa B expression. Conclusions Aberrant IL-32 alpha levels are participated in T2DM pathogenesis. IL-32 alpha potently induces Th17-related factors and amplifies the proliferative function of T cells.