Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity

Arthritis Res Ther. 2011 Jun 16;13(3):R88. doi: 10.1186/ar3363.

Abstract

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines.

Methods: We determined levels of IFN-λ1 mRNA in peripheral blood mononuclear cells (PBMC) and serum protein levels in patients with SLE using real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunoassay (ELISA). Further, we detected the concentration of IFN-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and interleukin-8 (IL-8) secreted by PBMC under the stimulation of IFN-λ1 using ELISA.

Results: IFN-λ1 mRNA and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IFN-λ1 mRNA and serum protein levels compared with those with inactive disease as well. Serum IFN-λ1 levels were positively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), anti-dsDNA antibody, C-reactive protein (CRP) and negatively correlated with complement 3. Serum IFN-λ1 levels were higher in SLE patients with renal involvement and arthritis compared with patients without the above-mentioned manifestations. IFN-λ1 with different concentrations displayed different effects on the secretion of the chemokines IP-10, MIG and IL-8.

Conclusions: These findings indicate that IFN-λ1 is probably involved in the renal disorder and arthritis progression of SLE and associated with disease activity. Moreover, it probably plays an important role in the pathogenesis of SLE by stimulating secretion of the chemokines IP-10, MIG and IL-8. Thus, IFN-λ1 may provide a novel research target for the pathogenesis and therapy of SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL9 / immunology
  • Chemokine CXCL9 / metabolism
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Female
  • Humans
  • Immunomodulation / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interferons
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism
  • Interleukins / blood*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Severity of Illness Index*
  • Young Adult

Substances

  • CXCL10 protein, human
  • CXCL8 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines
  • interferon-lambda, human
  • Interleukin-8
  • Interleukins
  • RNA, Messenger
  • Interferon-gamma
  • Interferons