The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

Ann Rheum Dis. 2013 Sep 1;72(9):1569-74. doi: 10.1136/annrheumdis-2012-202264. Epub 2012 Dec 25.


Background: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis.

Objective: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting.

Results: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation.

Conclusions: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.

Keywords: Arthritis; Cytokines; Inflammation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Psoriatic / metabolism*
  • Arthritis, Psoriatic / pathology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Female
  • Humans
  • Interleukin-1 / metabolism*
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology
  • Synovial Membrane / metabolism*


  • IL36A protein, human
  • Interleukin-1