Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis.
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Cronstein BN, Sunkureddi P
Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis.
J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790.
- PubMed ID
- 23319019 [ View in PubMed]
- Abstract
It has been recently demonstrated that interleukin 1beta (IL-1beta) plays a central role in monosodium urate crystal-induced inflammation and that the NALP3 inflammasome plays a major role in IL-1beta production. These discoveries have offered new insights into the pathogenesis of acute gouty arthritis. In this review, we discuss the molecular mechanisms by which monosodium urate crystals induce acute inflammation and examine the mechanisms of action (MOAs) of traditional anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids) and biologic agents (e.g., the IL-1beta antagonists anakinra, rilonacept, and canakinumab) to understand how their MOAs contribute to their safety profiles. Traditional anti-inflammatory agents may act on the IL-1beta pathway at some level; however, their MOAs are broad-ranging, unspecific, and biologically complex. This lack of specificity may explain the range of systemic adverse effects associated with them. The therapeutic margins of nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids are particularly low in elderly patients and in patients with cardiovascular, metabolic, or renal comorbidities that are frequently associated with gouty arthritis. In contrast, the IL-1beta antagonists act on very specific targets of inflammation, which may decrease the potential for systemic adverse effects, although infrequent but serious adverse events (including infection and administration reactions) have been reported. Because these IL-1beta antagonists target an early event immediately downstream from NALP3 inflammasome activation, they may provide effective alternatives to traditional agents with minimal systemic adverse effects. Results of ongoing trials of IL-1beta antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Rilonacept Interleukin-1 alpha Protein Humans UnknownBinderDetails Rilonacept Interleukin-1 beta Protein Humans UnknownBinderDetails Rilonacept Interleukin-1 receptor antagonist protein Protein Humans UnknownBinderDetails