Elevated serum interleukin-27 levels in patients with systemic sclerosis: association with T cell, B cell and fibroblast activation

Ann Rheum Dis. 2011 Jan;70(1):194-200. doi: 10.1136/ard.2009.121053. Epub 2010 Aug 12.

Abstract

Objective: To determine serum levels of interleukin 27 (IL-27) in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc.

Methods: Serum levels of IL-27 in 91 patients with SSc and the production of IL-27 by isolated monocytes were examined by ELISA. The expression of IL-27 receptor in the skin fibroblasts, B cells and T cells was quantified by real-time PCR. The effect of IL-27 on immunoglobulin G (IgG) production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts was also analysed.

Results: Serum IL-27 levels were raised in patients with SSc compared with healthy controls and correlated positively with the extent of skin and pulmonary fibrosis and immunological abnormalities. IL-27 levels also correlated positively with serum levels of hyaluronan, recently identified as an endogenous ligand for Toll-like receptors. The retrospective longitudinal analysis showed a tendency for serum IL-27 levels to be attenuated during the follow-up period. IL-27 production by cultured monocytes was increased by hyaluronan stimulation. IL-27 receptor expression was upregulated in the affected skin fibroblasts, B cells and CD4 T cells of patients with SSc. Moreover, IL-27 stimulation increased IgG production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts in patients with SSc compared with those in healthy controls.

Conclusion: These results suggest that IL-27 and its signalling in B cells, T cells and fibroblasts contributes to disease development in patients with SSc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Collagen / biosynthesis
  • Female
  • Fibroblasts / immunology*
  • Fibrosis / immunology
  • Follow-Up Studies
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / blood*
  • Interleukin-17 / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Receptors, Interleukin / metabolism
  • Scleroderma, Systemic / immunology*
  • Skin / immunology
  • Skin / pathology
  • Young Adult

Substances

  • IL27RA protein, human
  • Interleukin-17
  • Receptors, Interleukin
  • Collagen