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Serum IL-6 and sIL-6R in type 2 diabetes contribute to impaired capillary-like network formation.

We hypothesized that the serum from individuals with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) would reduce in vitro capillary-like network formation compared to normal glucose tolerance (NGT) serum, and that this would occur along with higher serum concentrations of inflammatory cytokines and lower concentrations of angiogenic growth factors. Subjects were sedentary, older (55-65 yrs) adults with NGT, IGT or T2DM (n=10/group) matched for BMI. HRVT-ECs or CAECs were used in a capillary-like network formation assay using endothelial basal medium supplemented with 7.5% serum. Quantification of HRVT-EC network length indicated that serum from the T2DM group resulted in 32% and 35% lower network formation than when using serum from the NGT and IGT groups, respectively (P<0.05). Serum from T2DM subjects resulted in CAEC network formation that was 11% and 8% lower than when using serum from NGT and IGT subjects, respectively (P<0.05). Analysis of serum cytokines indicated that IL-6 was 41% and 49% higher in the IGT and T2DM groups, respectively, compared with the NGT group (P<0.05) and there was a trend for higher sIL-6R (P=0.06) and IL-8 (P=0.08) in the T2DM serum compared to NGT. The use of recombinant IL-6 and sIL-6R at concentrations detected in the T2DM serum also reduced capillary network formation compared to NGT concentrations (P<0.05). These results suggest that IL-6 and sIL-6R present in the serum of T2DM individuals impair in vitro endothelial cell function across different cell lines. Our findings may have implications for the microvascular complications associated with T2DM.