Increased expression of interleukin-7 in labial salivary glands of patients with primary Sjögren's syndrome correlates with increased inflammation

Arthritis Rheum. 2010 Apr;62(4):969-77. doi: 10.1002/art.27318.

Abstract

Objective: To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome.

Methods: Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects.

Results: The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell-attracting and T cell-differentiating cytokines (monokine induced by interferon-gamma [IFNgamma], IFNgamma-inducible 10-kd protein, IL-12, and IL-15), as well as Th1 (IFNgamma), Th2 (IL-4), Th17 (IL-17A), proinflammatory (tumor necrosis factor alpha and IL-1alpha), and regulatory (IL-10 and IL-13) cytokine production by PBMCs. All of these cytokines were previously shown to be associated with primary SS. The IL-7-induced increase in IL-10 production in patients with primary SS was reduced compared with that in control subjects.

Conclusion: The correlation between LSG IL-7 expression and (local) disease parameters in primary SS as well as the IL-7-mediated induction of inflammatory cytokines indicate that IL-7 might contribute to the immunopathology of primary SS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Inflammation / epidemiology
  • Inflammation / physiopathology*
  • Interferon-gamma / immunology
  • Interleukin-7 / blood
  • Interleukin-7 / genetics*
  • Interleukin-7 / metabolism
  • Male
  • Middle Aged
  • Salivary Glands / pathology
  • Salivary Glands / physiopathology*
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / pathology
  • Sjogren's Syndrome / physiopathology*
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Interleukin-7
  • Interferon-gamma