Table 1 Factors regulating gouty inflammation as elucidated by recent research
Factors promoting acute inflammation in response to urate crystals | Factors limiting initiation of acute crustal-induced inflammation (with or without promoting resolution) | ||
|---|---|---|---|
Endogenous | Exogenous | Endogenous | Exogenous |
1st signal NLRP3 inflammasome activation: - C5a - GM-CSF - S100A8/A9 | 1st signal NLRP3 inflammasome activation: - Long chain saturated fatty acids (e.g., palmitate) - Spikes in systemic acetate levels (e.g., via alcohol) Angiotensin converting enzyme inhibition: (via kinin B1 receptors) | Nutritional biosensing: - AMPK activity - PPAR-γ activity Microbiome (via production of short chain fatty acids) | Inhibitors of NLRP3 inflammasome activation: - Omega-3 fatty acids - Ketogenic diet (via β-hydroxybutyrate) Dietary fiber and short chain fatty acids (e.g., acetate, butyrate) |
Genetic: - Common PPARGC1B risk allele A rs45520937 - Certain CARD8, CD14, ILB SNPs Epigenetic: - Certain Class I HDACs -miR-155 | – | Possible Genetic Factors Epigenetic: - miR-146a | – |
Other: - Changes in urate crystal morphology and surface constituents - Hyperuricemia (via decreased phagocyte autophagy and IL-1ra expression) - Leukocyte senescence | – | Other: - Crystal morphology and surface constituents - Some adaptive immune responses: effector CD41 T cells, IFN-1 - Certain cytokines and protease inhibitors - IL-37 (using MerTK signaling) - Alpha1 anti-trypsin - Some sequelae of PMN activation - Aggregated NET formation - Apoptosis, efferocytosis (including effects of AnnexinA1, Clec12a) - C5a-induced PMN microvesicles (via MerTK signaling) | – |