Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Centre for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa.
FEBS J. 2022 Feb;289(4):955-964. doi: 10.1111/febs.15807. Epub 2021 Mar 29.
Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD supplies. We hypothesize that an insufficient cellular NAD supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.
在感染过程中，巨噬细胞的代谢途径会发生分歧，特别是在氧化磷酸化和有氧糖酵解（Warburg 样代谢）之间切换。同时，巨噬细胞在交替激活和经典激活之间转换。在交替激活的巨噬细胞中上调的关键酶是吲哚胺 2,3-双加氧酶，它将色氨酸转化为犬尿氨酸，用于从头合成烟酰胺。烟酰胺可用于补充细胞 NAD 供应。我们假设细胞 NAD 供应不足是巨噬细胞代谢转变的根本原因。我们断言，烟酰胺途径的操纵可能纠正有害的免疫反应。我们建议评估烟酰胺（维生素 B3）及其类似物，包括异烟肼、烟酰胺单核苷酸和烟酰胺核苷，作为治疗败血症感染原因的潜在疗法，包括 COVID-19。
