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

Objective Modulation of TNF-a 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-α/TNFR system in various rheumatic diseases. Tumor necrosts factor-alpha (TNF-α) affects its target cells through binding to nvo different receptors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and cytotoxic effects of TNF-a on various cells have been reported. In Sjogren's syndrome (SS) focal sialadenitis leads to salivary gland destruction and loss of function, Although TNF-α is one possible mediator in these processes, nothing is known about the spatial distribution of TNF-a 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-α, TNFR-p55 and TNFR-p75. Results TNF-a, 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-a and TNFR expression. In addition, resident vascular endothelial cells, ductal epithelial cells and fibroblasts co-expressed TNF-a and TNFR. In contrast, acinar end piece cells did not express TNF-a or TNFR-p75 although TNFR-p55 was expressed. Conclusion The interrelated localization of TNF receptors and their ligand TNF-a in inflammatory and in endothelial cells suggests a proinflammatory role of TNF-a in SS. The expression of TNF-a 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-α/TNRF system argues against its role in acinar cell atrophy.