IL-1 family cytokines and soluble receptors in systemic lupus erythematosus

Arthritis Res Ther. 2018 Feb 8;20(1):27. doi: 10.1186/s13075-018-1525-z.


Background: Dysregulated production of cytokines has a critical role in systemic lupus. The aim of this work is to identify, by a comprehensive analysis of IL-1 family cytokines and receptors in serum, correlation between cytokines/receptors' levels and the clinical and serological features of the disease.

Methods: A full clinical evaluation was performed in 74 patients with systemic lupus erythematosus (SLE). C3, C4, anti-dsDNA and anti-C1q antibodies were measured. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein (IL-18BP)) were measured in serum by multiarray ELISA. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Data were analysed by non-parametric tests and by multivariate analysis, using partial least squares (PLS) models.

Results: Total IL-18, IL-18BP, sIL-1R4 and IL-1Ra levels were higher in SLE vs.

Controls: Total and free IL-18 and sIL-1R4 were higher in patients with active vs. inactive disease and correlated with ECLAM, anti-C1q and anti-dsDNA antibodies. sIL-1R2 was higher in patients with inactive disease, was negatively correlated with ECLAM and anti-C1q antibodies and was positively correlated with C3 levels. PLS identified sIL-1R4, sIL-1R2 and anti-dsDNA as variables distinguishing patients with active from those with inactive disease; sIL-1R4, IL-18BP and anti-dsDNA identified patients with active nephritis; sIL-1R4, C3, IL-18 and free IL-18 identified patients with haematological involvement.

Conclusion: The data support the use of IL-18, sIL-1R2 and sIL-1R4 as biomarkers of disease activity and organ involvement, and suggest that failure in the inhibition of IL-1 activation may be a critical event in the active stages of SLE.

Keywords: Biomarkers; Il-1 family; Soluble IL-1 family receptors; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin-1 / blood*
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Protein Isoforms / blood
  • Receptors, Interleukin-1 / blood*


  • Autoantibodies
  • Biomarkers
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Protein Isoforms
  • Receptors, Interleukin-1