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Abstract: TH-PO510

Interleukin 6 plus High Salt Increases Functional Epithelial Sodium Channel Activity

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic


  • Wynne, Brandi M., Emory University School of Medicine, Atlanta, Georgia, United States
  • Buncha, Vadym, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
  • Cherezova, Alena, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
  • McCarthy, Cameron G., Augusta University, Augusta, Georgia, United States
  • Hecht, Gillian Grace, Emory University, Atlanta, Georgia, United States
  • Wenceslau, Camilla F., The University of Toledo, Toledo, Ohio, United States
  • Hoover, Robert S., Emory University, Atlanta, Georgia, United States
  • Mamenko, Mykola, Augusta University, Augusta, Georgia, United States

Hypertension (HTN) is characterized by increased sodium (Na+) reabsorption, and increased cytokines such as interleukin 6 (IL6). Our data suggests that IL6 infusion increases blood pressure (BP) and distal nephron Na+ transporter expression/activity, with an early reduction in urinary Na+ excretion (UNa). However, whether this reduction in UNa is mediated by epithelial sodium channel (ENaC) activity is unknown. We hypothesize that IL6 increases ENaC activity.


Mice were treated with IL-6 (16ng/hr, 0.1%BSA) or vehicle via osmotic minipump, and fed high salt (HS, 4%) diet for 1 or 3 days (1D, 3D). ENaC open probability (Po), functional expression (fN) and functional activity (fNPo) were assessed in split open tubules (cortical collecting duct, CCD) from IL6-treated (IL6+HS) and vehicle (HS) mice. Data are expressed as mean±SEM, where SEM is patch number in at least 3 mice per group.


We observed a trending increase in ENaC fN in CCD from IL6+HS after only 1D, reaching significance by 3D (0.94±0.14, n=44 vs.0.63±0.08, n=63, p<0.05), compared to HS only. Although open probability (Po) was not increased, fNPo was almost doubled in IL6+HS treated mice after 1D (0.24±0.08, n=51 vs. 0.12±0.04, n=62), and significantly increased after 3D (0.28±0.07, n=44 vs. 0.13±0.04, n=63, p<0.05).


Here, we show that increased IL6 causes trending increases in ENaC fN and fNPo, after only 1D. These data correlate with our data showing UNa is reduced in the first 24 hours. Continued IL6+HS treatment significantly increased both fN and fNPo by day 3, also correlating with increases in ENaCα/γ expression and BP (by D3). We later see increased UNa, indicating pressure natriuresis. These data suggest that, remarkably, IL6 may activate distal nephron Na+reabsorption, even with increased dietary salt. These data reveal a novel role for IL6-mediated changes in UNa excretion, leading to salt-sensitive HTN.

Figure 1. Representative continuous current traces from cell-attached patches in CCD.


  • NIDDK Support