What makes gouty inflammation so variable?

Abstract

Acute gout arthritis flares contribute dominantly to gout-specific impaired health-related quality of life, representing a progressively increasing public health problem. Flares can be complex and expensive to treat, partly due to the frequent comorbidities. Unmet needs in gout management are more pressing given the markedly increasing gout flare hospital admission rates. In addition, chronic gouty arthritis can cause joint damage and functional impairment. This review addresses new knowledge on the basis for the marked, inherent variability of responses to deposited urate crystals, including the unpredictable and self-limited aspects of many gout flares. Specific topics reviewed include how innate immunity and two-signal inflammasome activation intersect with diet, metabolism, nutritional biosensing, the microbiome, and the phagocyte cytoskeleton and cell fate. The paper discusses the roles of endogenous constitutive regulators of inflammation, including certain nutritional biosensors, and emerging genetic and epigenetic factors. Recent advances in the basis of variability in responses to urate crystals in gout provide information about inflammatory arthritis, and have identified potential new targets and strategies for anti-inflammatory prevention and treatment of gouty arthritis.

Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome

“…Gouty inflammation is characterized by intense pain caused by the deposition of MSU crystals into the articular joint and surrounding tissues [25]. Uptake of MSU crystals by macrophages induces proinflammatory cytokine and chemokine productions, which leads to the further recruitment of immune cells into the joint and escalates the inflammation [25,26]. The current therapeutic approaches against gouty inflammation are given mainly to reduce hyperuricaemia and inflammatory status [25].…”

Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia

“…Gout is no longer viewed solely as an articular disease and, in its most comprehensive definition, it is an inflammatory and metabolic disorder as the manifestations of gout extend beyond the local inflammatory consequence of MSU crystal deposition . Hyperuricemic patients exhibit higher incidence of comorbidities such as cardiovascular disease, type 2 diabetes, metabolic syndrome, chronic kidney disease, cancer, and premature aging (Figure ) .…”

“…Gout is no longer viewed solely as an articular disease and, in its most comprehensive definition, it is an inflammatory and metabolic disorder as the manifestations of gout extend beyond the local inflammatory consequence of MSU crystal deposition. 119 Hyperuricemic patients exhibit higher incidence of comorbidities such as cardiovascular disease, type 2 diabetes, metabolic syndrome, chronic kidney disease, cancer, and premature aging (Figure 3). [6][7][8][9][10] Whether urate elevation is involved in the pathogenesis of comorbidities seen in gout is still a debated issue, but an increasing number of epidemiological studies have found hyperuricemia as an independent risk factor for gout comorbidities: A meta-analysis including cohorts of over a million subjects shows serum urate levels to increase cardiovascular mortality risk in a dose-dependent manner, and experimental animal models show positive correlation between urate levels, arterial hypertension, and insulin resistance, with reversal of manifestation upon lowering and inhibition of urate.…”

Retracted: Skin‐patch of Xin Huang Pian on relieving joint symptoms in patients with acute gouty arthritis: A Randomized, Double‐Blind, Active‐Controlled Trial

“…The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) guidelines for the pharmacologic management of acute gouty arthritis include administration of oral colchicine, non‐steroidal anti‐inflammatory drugs (NSAIDs), corticosteroids and interleukin (IL)‐1 blockers (Khanna et al, 2012b, Wang et al, 2018). However, responses to these oral agents often take at least 12–24 hr to commence and can take from several days to a week to be take complete effect (Terkeltaub, 2017). So, patients with acute gouty arthritis will benefit from an alternative therapy that can work quickly to relieve pain.…”