Abstract: TH-PO407

Erythropoietin (Epo) Inhibits Sodium-Driven Pro-Inflammatory Effects

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Angeletti, Andrea, Icahn School of Medicine at Mount Sinai, New York, United States
  • Donadei, Chiara, Icahn School of Medicine at Mt. Sinai, New York, United States
  • D'Agati, Vivette D., Columbia University College of Physicians and Surgeons, New York, New York, United States
  • Fribourg, Miguel L, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • La Manna, Gaetano, DIMES, Bologna, Italy
  • Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

High sodium concentrations promote T cell IL-17 production and injury by increasing intracellular pSGK1. We tested whether EPO, which we previously showed has immune-modulating effects, can counteract sodium-induced human Th17 production in vitro, and in a murine kidney disease model, in which sodium and EPO concentrations are elevated.

Methods

We added EPO or vehicle to human PBMC (n=3-8 donors per experiment) cultured in vitro +/- high [NaCl] or [urea] (osmotic control) and measured T cell proliferation, IL-17/IFNg production, pSGK1 (flow cytometry) and Foxp3 expression. To assess in vivo effects we fed WT B6 mice with normal or high NaCl diet, treated them aristolochic acid (ArA) to induce T cell-mediated interstitial nephritis ± EPO and measured proteinuria and immune responses 6 weeks later.

Results

EPO (but not urea) inhibited human NaCl-driven SGK1 phosphorylation, T cell proliferation (Fig. 1A), and IFNg production (6.7±1.2% vs. 1.8±0.4%, vehicle vs. EPO in the presence of NaCl; P<0.05), without affecting apoptosis/necrosis. EPO prevented Na-driven Th17 induction (1.6±0.3% vs. 0.7±0.3%, vehicle vs. EPO; P<0.05) and increased CD4+CD25+Foxp3+ Treg induction/function (Fig. 1B), while maintaining Treg stability. In mice fed a normal or a high NaCl diet, EPO reduced ArA-induced splenic Th1 and Th17 cells, increased Treg and reduced proteinuria (Fig. 1C).

Conclusion

EPO inhibits NaCl-induced proinflammatory T cell immunity in vitro and in vivo, in humans and mice. Our data support the concept of EPO is an immune-modulatory hormone that could physiologically counteract the proinflammatory effects of high intrarenal [NaCl].