Dihydronicotinamide Riboside Promotes a Pro-Inflammatory Macrophage Phenotype: Preclinical Findings

Synopsis

This study explored how various NAD precursors—including nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide (NAM), and a newer compound called NRH—influence the behavior of macrophages, immune cells that control inflammation. Researchers found that while all compounds can boost NAD+ levels, NRH was the most powerful, causing a sharp rise in NAD+ in both human and mouse macrophages. However, this strong boost also triggered inflammation, increasing the expression of cytokines and chemokines and enhancing the macrophage response to immune challenges like lipopolysaccharide (LPS). Blocking certain enzymes and signaling pathways, including IKK and ENT transporters, prevented NRH’s effects, suggesting these mechanisms regulate how NAD metabolism influences immunity. Overall, the findings reveal that different NAD boosters have distinct impacts on immune function, and that NRH may reprogram macrophages toward a pro-inflammatory state, which could be relevant for both inflammatory diseases and cancer research.

Journal

Frontiers in Immunology