Regulation of crystal induced inflammation: current understandings and clinical implications

ABSTRACT

Introduction: Accumulation of abnormal crystals in the body, derived from endogenous or exogenous materials can drive a wide spectrum of inflammatory disease states. It is well established that intra-articular deposition of monosodium urate (MSU) and calcium pyrophoshate (CPP) crystals contributes to joint destruction through pro-inflammatory processes.

Areas covered: This review will focus on current understanding and recent novelty about the mechanisms and the clinical implications of the inflammation induced by MSU and CPP crystals.

Expert opinion: Advances in molecular biology reveal that at the base of the inflammatory cascade, stimulated by MSU or CPP crystals, there are many complex cellular mechanisms mainly involving the NLRP3 inflammasome, the hallmark of autoinflammatory syndromes. The extensive studies carried out through in vitro and in vivo models along with a better clinical definition of the disease has led to an optimized use of existing drugs and the introduction of novel therapeutic strategies. In particular, the identification of IL-1 as the most important target in gout and pseudogout has made it possible to expand the pharmacological indications of anti-IL-1 biological drugs, opening new therapeutic perspectives for patients.

KEYWORDS:

• CPP crystals
• gout
• IL-1 inhibitors
• inflammation
• MSU crystals
• NLRP3 inflammasome

Article highlights

• Accumulation of abnormal crystals derived from endogenous or exogenous materials drive a wide spectrum of inflammatory disease states

• Inflammatory cytokines, in particular IL-1β, are the key mediators of crystal-induced inflammation

• The NLRP3 inflammasome is the major pathway through which crystals trigger the cellular inflammatory response

• The resolution of crystal-induced inflammation is a self-occurring event and is tightly regulated

• Chronic inflammatory response to crystal deposition results, in turn, into structural damage of the joints

• Effective treatments are available to suppress crystal-induced inflammation

• New and safer treatments based on new targets are under investigation

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was supported by the University of Padova, grant number DOR2051714/20 to FO.