Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis

Arthritis Rheum. 1994 May;37(5):644-52. doi: 10.1002/art.1780370507.


Objective: To quantify interleukin-1 receptor antagonist (IL-1ra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells.

Methods: IL-1 alpha, IL-1 beta, and IL-1ra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-1ra (sIL-1ra) and the alternatively spliced intracellular form (icIL-1ra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques.

Results: IL-1 alpha, IL-1 beta, and IL-1ra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the 10-100-fold excess of IL-1ra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-1ra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-1ra but secreted little IL-1ra into the culture supernatants. RT-PCR showed that icIL-1ra mRNA was more abundant than sIL-1ra mRNA in FLS and unfractionated ST cells.

Conclusion: IL-1ra production by RA ST cells is deficient relative to total production of IL-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / immunology
  • Base Sequence
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Humans
  • Immunoassay
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Molecular Sequence Data
  • Osteoarthritis / genetics
  • Osteoarthritis / immunology
  • RNA, Messenger / analysis
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Synovial Membrane / chemistry*
  • Synovial Membrane / immunology


  • Interleukin-1
  • RNA, Messenger
  • Receptors, Interleukin-1