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The concept of interleukin-1 (IL-1) as a target in osteoarthritis (OA) has been an attractive one for many years. It is a highly potent inducer of cartilage degradation, causing the induction of mRNA and controlling the bioavailability of disease-relevant proteases such as ADAMTS5 and MMP13. It drives synovitis and can induce other disease-relevant genes such as nerve growth factor, a key pain sensitiser in OA. However, the quality of evidence for its involvement in disease is modest. Descriptive studies have demonstrated expression of IL-1α and β in OA cartilage and elevated levels in the synovial fluid of some patients. Agnostic transcriptomic and genomic analyses do not identify IL-1 as a key pathway. In vivo models show a conflicting role for this molecule; early studies using therapeutic approaches in large animal models show a benefit, but most murine studies fail to demonstrate protection where the ligands (IL-1α/β), the cytokine activator (IL-1-converting enzyme), or the receptor (IL-1R) have been knocked out. Recently, a number of large double-blind randomised controlled clinical studies targeting IL-1 have failed. Enthusiasm for IL-1 as a target in OA is rapidly dwindling.

Original publication

DOI

10.12688/f1000research.18831.1

Type

Journal article

Journal

F1000res

Publication Date

2019

Volume

8

Keywords

Interleukin-1, cartilage, catabolin, osteoarthritis, Animals, Cartilage, Articular, Double-Blind Method, Humans, Interleukin-1, Mice, Molecular Targeted Therapy, Osteoarthritis, Randomized Controlled Trials as Topic, Synovitis