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Treating inflammation by blocking interleukin-1 in humans.

Charles A Dinarello1, Jos W M van der Meer2

  • 1Department of Medicine, University of Colorado Denver, Aurora, CO, United States; Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Seminars in Immunology
|November 27, 2013
PubMed
Summary

Interleukin-1 (IL-1) blockade effectively treats inflammatory diseases. Targeting IL-1 reduces disease severity and improves patient outcomes in conditions like heart failure and gout.

Keywords:
AOSDAutoimmuneAutoinflammatoryC-reactive proteinCAPSCRPDIRAFCASFMFHIDSInflammationNLRP12NLRP3NOMIDPAPAPASHPFAPASAPHOSJIATNF receptor associated periodic syndromeTRAPSadult onset Still's diseasecryopyrin autoinflammatory periodic syndromesdeficiency of IL-1Rafamilial Mediterranean feverfamilial cold autoinflammatory syndromehyper IgD syndromeneonatal onset multi-inflammatory diseasesnucleotide-binding domain and leucine-rich repeat pyrin containing 12nucleotide-binding domain and leucine-rich repeat pyrin containing 3periodic fever, aphthous stomatitis, pharyngitis, and adenitispyoderma-gangrenosum, acne, and suppurativa hidradenitispyogenic arthritis, pyoderma gangrenosum, and acnesynovitis, acne, pustulosis, hyperostosis and osteitissystemic-onset juvenile idiopathic arthritis

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Area of Science:

  • Immunology
  • Inflammation Biology
  • Pharmacology

Background:

  • Interleukin-1 (IL-1) is a key cytokine in local and systemic inflammation.
  • IL-1's role in disease pathogenesis is increasingly recognized, leading to targeted therapies.
  • Previous attempts to boost immune responses with IL-1 in cancer patients caused significant toxicity.

Purpose of the Study:

  • To evaluate the efficacy of pharmacological IL-1 blockade in inflammatory diseases.
  • To highlight the benefits of reducing IL-1 activity in various clinical conditions.
  • To review approved and investigational IL-1 targeting therapies.

Main Methods:

  • Review of clinical data on IL-1 targeting therapies.
  • Analysis of the impact of IL-1 blockade on disease severity.
  • Examination of approved IL-1 inhibitors: anakinra, rilonacept, and canakinumab.

Main Results:

  • Monotherapy with IL-1 blockers provides rapid and sustained reduction in inflammatory disease severity.
  • IL-1 blockade is effective in common conditions such as heart failure and gout arthritis.
  • Approved therapies include IL-1 receptor antagonist (anakinra), decoy receptor (rilonacept), and anti-IL-1β antibody (canakinumab).

Conclusions:

  • Specific pharmacological blockade of IL-1 is a beneficial therapeutic strategy.
  • Reducing IL-1 activity significantly alleviates disease burden for many patients.
  • Ongoing research includes monoclonal antibodies targeting the IL-1 receptor and IL-1α.