Arguments for interleukin 1 as a target in chronic arthritis

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• Tumour necrosis factor (TNF) and interleukin 1 (IL1) are master cytokines in chronic destructive arthritis.
• Current therapies for rheumatoid arthritis (RA) primarily target TNF, but are not universally effective.
• IL1 production is consistently observed in RA synovial biopsies, suggesting TNF-independent pathways.

Purpose of the Study:

• To investigate the role of IL1 in arthritis pathogenesis, particularly in relation to TNF.
• To evaluate IL1 as a therapeutic target in chronic destructive arthritis.

Main Methods:

• Analysis of cytokine patterns in synovial biopsy specimens from RA patients.
• Studies using experimental arthritis models in mice, including IL1b deficient mice.
• Comparison of anti-TNF and anti-IL1 treatment efficacy in experimental models.

Main Results:

• IL1b staining is present in 100% of early RA synovial biopsies, while TNF staining is found in 50%.
• TNF induces arthritis primarily through IL1 induction; TNF alone is not destructive.
• TNF-independent IL1 production occurs in many experimental arthritis models.
• Anti-IL1 treatment shows greater efficacy than anti-TNF treatment.
• IL1b deficient mice lack chronic, erosive arthritis.
• IL1b is crucial for chronic arthritis and cartilage erosion, but not necessarily early joint swelling.

Conclusions:

• IL1b is a critical mediator of chronic arthritis and cartilage erosion.
• IL1b represents a more attractive therapeutic target than TNF for chronic, destructive arthritis.
• Targeting IL1 may overcome limitations of anti-TNF therapies in RA.