New Study Reveals How NAD⁺ Protects Against Deadly Septic Shock

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PASADENA, Calif. — February 19, 2024 — A groundbreaking study co-authored by Dr. Abdallah (Abdala) Elkhaland Dr. Anju Vasudevan of Huntington Medical Research Institutes (HMRI) identifies a novel mechanism through which nicotinamide adenine dinucleotide (NAD⁺) protects the body from septic shock, one of the most severe and life-threatening immune reactions.

Published in eLife, the paper — “NAD⁺ Prevents Septic Shock–Induced Death by Non-Canonical Inflammasome Blockade and IL-10 Cytokine Production in Macrophages” — demonstrates that NAD⁺ not only blocks key inflammatory pathways that drive septic shock but also promotes an anti-inflammatory immune response that restores balance to the immune system.

The international research team — Jasper Iske, Rachid El Fatimy, Yeqi Nian, Amina Ghouzlani, Siawosh K. Eskandari, Hector Rodriguez, Cetina Biefer, Anju Vasudevan, and Abdallah Elkhal — discovered that:

  • NAD⁺ treatment protected mice from bacterial and LPS-induced endotoxic shock, dramatically improving survival.

  • The compound blocked activation of the non-canonical inflammasome, reducing production of IL-1β and IL-18 and preventing pyroptotic cell death through the caspase-11/Gasdermin-D pathway.

  • At the same time, NAD⁺ enhanced IL-10 cytokine signaling, promoting immune homeostasis independently of inflammasome inhibition.

“These dual protective effects — both blocking excessive inflammation and activating anti-inflammatory pathways — underscore NAD⁺’s unique therapeutic potential for treating septic shock,” said Dr. Elkhal, Assistant Professor of Immunology and Head of HMRI’s Neuro-Cardio-Immunology Laboratory.

The findings open new possibilities for metabolic immunotherapy, where naturally occurring cellular metabolites like NAD⁺ could be repurposed to treat severe inflammatory diseases.

Full article: eLife, February 2024