The NLRP3 inflammasome - interleukin 1 pathway as a therapeutic target in gout

Zoltán Szekanecz; Szilvia Szamosi; Gergő E Kovács; Elek Kocsis; Szilvia Benkő

doi:10.1016/j.abb.2019.01.031

The NLRP3 inflammasome - interleukin 1 pathway as a therapeutic target in gout

Arch Biochem Biophys. 2019 Jul 30:670:82-93. doi: 10.1016/j.abb.2019.01.031. Epub 2019 Jan 30.

Authors

Zoltán Szekanecz¹, Szilvia Szamosi¹, Gergő E Kovács², Elek Kocsis², Szilvia Benkő³

Affiliations

¹ Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
² Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
³ Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: benkosz@med.unideb.hu.

PMID: 30710503
DOI: 10.1016/j.abb.2019.01.031

Abstract

The NLRP3 inflammasome is implicated in the processing of the pro-inflammatory cytokine interleukin 1β. Inflammatory disorders associated with the activation of the NLRP3 inflammasome - IL-1 axis are termed autoinflammatory diseases. Gout is an autoinflammatory disease, which is triggered by the deposition of monosodium urate crystals of precipitated uric acid. It is characterized by recurrent attacks of inflammation due to the activation of phagocytic cells that try to clear the crystals. NLRP3 inflammasome-mediated IL-1β production plays a key role in the manifestation of the disease. Currently, the best approach to treat gout is to reduce uric acid concentration by targeting xanthine oxidase or uric acid transporters, or to use non-steroidal anti-inflammatory drugs. Nevertheless, most of these treatments are not effective enough and may results in side effects. During the past decades, our knowledge has greatly improved about the molecular mechanisms of NLRP3 activation. This knowledge enables and urges scientists to discover or design drugs that target pathways of NLRP3 inflammasome activation, or more preferentially, NLRP3 inflammasome itself. In this review, we discuss the already available drugs and products, that target the diverse pathways of the NLRP3 - IL-1β axis, and the future therapeutic perspectives.

Keywords: Autoinflammatory disease; Gout; Inflammasome; Interleukin 1; NLRP3.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Gout / drug therapy*
Gout / metabolism
Humans
Inflammasomes / metabolism*
Interleukin-1 / metabolism*
Molecular Targeted Therapy / methods*
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*

Substances

Inflammasomes
Interleukin-1
NLR Family, Pyrin Domain-Containing 3 Protein