Administration of NMN protects against damaging inflammation in mice modeling colitis.
Inflammation is at the root of the vital immune response to invaders. First, inflammation activates, recruiting an army of immune cells to destroy harmful bacteria or viruses (pathogens). However, inflammation must eventually deactivate because persistent and excessive inflammation can lead to diseases, such as asthma and inflammatory bowel diseases (IBD).
Researchers from Ajou University School of Medicine in Korea have helped clarify the mechanisms underlying inflammation and colitis, finding that levels of NAD+ – a compound critical for cellular energy – are linked to colitis severity in mice. In a study published in Redox Biology, mice lacking NAMPT in immune cells called macrophages, the enzyme that produces an NAD+ precursor called NMN, showed increased colitis severity in response to inflammation as well as decreased survival. These effects, both disease severity and survival, could be rescued by injecting the mice with NMN (500 mg/kg) three times over the course of a week. These findings suggest that NAMPT-dependent NAD+ biosynthetic pathway activation may treat inflammatory diseases like IBD.
Finding the inflammatory balance
Our guts are metabolic metropolises filled with sprawling populations of microbes and cells. One such cell, the macrophage, plays a crucial role in fine-tuning the intestinal mucosal immune system. These intestinal macrophages function to clear pathogens, bacterial wall components, and dying cells.
However, failure to mount a robust protective response against pathogens during the resolution phase of inflammation may lead to persistent and excessive inflammation, as often observed in IBD. Additionally, accumulating evidence suggests that enforcing inflammatory resolution in macrophages might represent a novel therapeutic approach for controlling intestinal inflammation and restoring tissue function.