Inflammasome and IL-1beta-mediated disorders

Our plain-English summary of Inflammasome and IL-1beta-mediated disorders, by H.M. Hoffman, A.A. Wanderer (Current Allergy and Asthma Reports, 2010).

The study

• Authors: H.M. Hoffman, A.A. Wanderer
• Journal: Current Allergy and Asthma Reports
• Published: 2010;10(4):229-35
• Type of article: Review
• Cited by: 126 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The NLRP3 inflammasome is an intracellular complex that regulates the release of proinflammatory cytokines such as interleukin-1beta in response to exogenous pathogens and endogenous danger signals. Evidence from studies involving human genetics, human ex vivo mononuclear cell responses, and in vivo and in vitro murine models confirms the importance of the inflammasome and interleukin-1beta in the pathogenesis of several inherited and complex diseases. The availability of several effective interleukin-1beta targeted therapies has allowed for successful proof-of-concept studies in several of these disorders. However, many other diseases are likely to be mediated by the inflammasome and interleukin-1beta, providing additional targets in the future.

In plain English

This article was a narrative review, not a new study. The authors described the NLRP3 inflammasome, a protein complex inside cells that controls release of the inflammatory signal interleukin-1 beta (IL-1β). They surveyed published research on diseases linked to IL-1β and on drugs that block it. For the inherited cryopyrinopathies, they reported that earlier trials of IL-1β-blocking drugs succeeded and led to US Food and Drug Administration approval. They wrote that several studies supported such treatment in refractory gout. Asbestos was discussed briefly, in one section and a table entry on silicosis and asbestosis, which the authors called occupational-related disorders marked by inflammatory cells and interstitial fibrosis. Citing an earlier study, they wrote that the chronic course of these diseases is thought to involve several pathways, including IL-1β release when silica and asbestos stimulate the NLRP3 inflammasome. They listed silicosis and asbestosis among diseases being considered for IL-1β-blocking treatment, not among those already treated with it. The authors concluded that IL-1 blocking treatment is now used successfully in other disorders they reviewed, such as the cryopyrinopathies. For silicosis and asbestosis, they gave only a rationale for treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on diseases linked to the NLRP3 inflammasome and IL-1β, and on IL-1β targeted therapy
• Who was studied: No study population. The review covered published work on inherited and complex inflammatory diseases, including cryopyrinopathies, gout, type 2 diabetes, bleomycin lung injury, silicosis and asbestosis, and others. No number of studies or search method is given.
• Exposure: Asbestos and silica, discussed as stimuli of the NLRP3 inflammasome in silicosis and asbestosis. No fiber types are named. The review also covered other triggers such as uric acid/urate crystals and bleomycin.
• Main results:
  • Silicosis and asbestosis: the authors described the chronic tissue changes as neutrophils, monocytes and other inflammatory cells with interstitial fibrosis. Citing an earlier study (their reference 17), they wrote that the chronicity is thought to result from several pathways, including IL-1β secretion when silica and asbestos stimulate the NLRP3 inflammasome.
  • Silicosis and asbestosis were listed under complex diseases being considered for IL-1β targeted therapy, not under diseases already successfully treated with it. The authors wrote that there is a rationale for such treatment.
  • Cryopyrinopathies (inherited inflammatory disorders): the authors reported that earlier trials of IL-1β targeted therapy were successful and led to US Food and Drug Administration approval.
  • Gout: the authors wrote that results from several earlier studies support IL-1β targeted therapy as beneficial in refractory acute and chronic gout.
• The authors' conclusion: The authors concluded that the inflammasome and IL-1β have been implicated in rare inherited and more common complex diseases. They also concluded that IL-1 targeted therapy is now being used successfully with a significant impact on patients' lives. That success refers to disorders already treated with it, such as the cryopyrinopathies, not to silicosis or asbestosis, for which the authors offered only a treatment rationale.

Topics

Medical terms in this study, explained in our Lexicon: Cytokine.

Related studies

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