Tumor necrosis factor-alpha and receptors for it in labial salivary glands in Sjögren's syndrome

Clin Exp Rheumatol. Mar-Apr 2001;19(2):131-7.


Objective: Modulation of TNF-alpha by neutralizing antibodies, soluble receptors and TNFR: Fc fusion proteins are being developed for the therapeutic modulation of immune inflammation. It is becoming increasingly important to understand the state and involvement of the TNF-alpha/TNFR system in various rheumatic diseases. Tumor necrosis factor-alpha (TNF-alpha) affects its target cells through binding to two different receptors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and cytotoxic effects of TNF-alpha on various cells have been reported. In Sjögren's syndrome (SS) focal sialadenitis leads to salivary gland destruction and loss of function. Although TNF-alpha is one possible mediator in these processes, nothing is known about the spatial distribution of TNF-alpha in relation to its receptors/target cells in salivary gland tissue.

Methods: Labial salivary glands (LSG) were obtained from 16 SS patients and 13 healthy controls and stained using the immunohistochemical peroxidase-anti-peroxidase (PAP) method for TNF-alpha, TNFR-p55 and TNFR-p75.

Results: TNF-alpha, TNFR-p55 and TNFR-p75 staining was absent, weak or relatively inextensive in controls compared to SS patients. Infiltrating mononuclear inflammatory cells in SS patients displayed moderate to strong TNF-alpha and TNFR expression. In addition, resident vascular endothelial cells, ductal epithelial cells and fibroblasts co-expressed TNF-alpha and TNFR. In contrast, acinar end piece cells did not express TNF-alpha or TNFR-p75 although TNFR-p55 was expressed.

Conclusion: The interrelated localization of TNF receptors and their ligand TNF-alpha in inflammatory and in endothelial cells suggests a proinflammatory role of TNF-alpha in SS. The expression of TNF-alpha and its receptors in fibroblasts and ductal cells may contribute to ductal hyperplasia and glandular fibrosis. However, in contrast to expectations, the cellular localization of the TNF-alpha/TNRF system argues against its role in acinar cell atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis*
  • Antigens, CD / immunology
  • Apoptosis / immunology
  • Atrophy
  • Biopsy
  • Humans
  • Immunoenzyme Techniques
  • Receptors, Tumor Necrosis Factor / analysis*
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor, Type II
  • Salivary Glands / chemistry*
  • Salivary Glands / immunology
  • Salivary Glands / pathology
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / immunology


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha