Abstract: TH-PO415

Oral NaHCO3 Activates the Splenic Anti-Inflammatory Pathway Promoting M2-Macrophage Polarization

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • O'Connor, Paul, Augusta University, Augusta, Georgia, United States
  • Baban, Babak, Augusta University, Augusta, Georgia, United States
  • Ray, Sarah C, Augusta University, Augusta, Georgia, United States
  • Tucker, Matthew, Augusta University, Augusta, Georgia, United States
  • Harris, Ryan A, Augusta University, Augusta, Georgia, United States
Background

Oral sodium bicarbonate (NaHCO3) may slow decline in kidney function in CKD, yet the mechanisms mediating this beneficial effect remain unclear. In the current study we tested the hypothesis that oral NaHCO3 intake promotes anti-inflammatory-M2 macrophage polarization by activating the splenic anti-inflammatory pathway in both rats and humans.

Methods

8-10 week old male Sprague Dawley rats maintained on a standard pellet diet with water ad libitum were utilized. To determine the effect of oral NaHCO3 on macrophage polarization, drinking water was replaced with solutions of NaHCO3 in tap water containing (0, 0.01, 0.05 or 0.1M NaHCO3; n=3 per treatment group) with all solutions made equimolar (0.1M) with the addition of NaCl. Following 4 days of drinking NaHCO3, rats were anesthetized, the left kidney and spleen harvested and prepared for flow cytometry analysis.
In a separate study, 7 healthy volunteers were given a single dose of NaHCO3 following an overnight fast. Venous blood was drawn for flow cytometry analysis, at baseline and 1 and 2 hours following ingestion of 2g of NaHCO3 in 250 ml of bottled water.

Results

We found that addition of NaHCO3 to the drinking water of rats resulted in a dose dependent increase in renal macrophage polarization away from an M1 (inflammatory) and toward an M2 (anti-inflammatory) phenotype with as little as 3 days of drinking 0.01M NaHCO3 solution (PDOSE=0.02). Most of the polarization effect could be attributed to an increase in renal M2 macrophages, with the % of renal cells identified as M2’s increasing from 2% to 8% at the highest dose of NaHCO3 (0.1M; PDOSE=0.006). The effect of 0.1M NaHCO3 on renal macrophage polarization was confirmed in a separate group of rats (n=5/5; P=0.007) and was abolished with prior splenectomy.
In human blood, T-cells were reduced from 15.6±0.8 at baseline to 13.0±0.8% of all leukocytes at 2 hours post NaHCO3 ingestion; (P=0.01). Inflammatory cells, M1 macrophages (P=0.054) and Th17+ cells (P=0.06), tended to decrease, whereas, M2 macrophages tended to increase from 48.4±1.2 at baseline to 50.9±0.4% of all macrophages 2 hours post NaHCO3 (p=0.054).

Conclusion

Our data indicate that oral NaHCO3 may activate the splenic anti-inflammatory pathway in rats and humans. Activation of these pathways may underlie part of the beneficial effects of NaHCO3 observed in CKD patients.

Funding

  • NIDDK Support