Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies

Gregory Livshits*, A. Kalinkovich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


Background Chronic inflammatory arthropathies, such as rheumatoid arthritis (RA), spondyloarthritis, including psoriatic arthritis (PsA), ankylosing spondyloarthritis (AS), osteoarthritis (OA), and intervertebral disc degenerative disease (DDD) constitute major public health problems that are anticipated to grow significantly as the human population ages. However, many aspects concerning the molecular mechanisms underlying their onset and progression remain unclear. Design This narrative review critically analyzes the molecular mechanisms underlying the inflammation-associated pathogenesis of the aforementioned joint diseases. This includes, in particular, the major role played by several key soluble factors (such as cytokines and the associated signaling pathways, designated as “fragile nodes”) produced by local cells and recruited to the joints' immune cells, whose elimination by specific drugs has dramatically improved the diseases' symptomatology and outcome in human clinical trials or in rodent arthritis models. Hypothesis and the aim of this review We hypothesize that the pathogenesis of chronic inflammatory arthropathies is governed by hierarchical, imbalanced pro-inflammatory cytokine networks (HIPICNs) (comprising a combination of fragile nodes) that are created during the development of both autoimmune (RA, PsA, and AS) and non-autoimmune (OA and DDD) disorders. The main aim of this review is to provide evidence that despite substantial pathobiological differences between these arthropathies, the HIPICNs created are quite common, thus justifying the merging of these disorders mechanistically and suggesting that these common mechanisms exist in the onset and progression of different joint diseases.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
JournalOsteoarthritis and Cartilage
Issue number1
StatePublished - Jan 2018


FundersFunder number
Israel Science Foundation1018/13


    • Cytokine network
    • Disc degenerative disease
    • Inflammation
    • Osteoarthritis
    • Rheumatoid arthritis
    • Spondyloarthritis


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