Tumor necrosis factor-alpha and receptors for it in labial salivary glandsin Sjogren's syndrome

Objective Modulation of TNF-alpha by neutralizing antibodies, soluble receptor and TN FR: Fc fusion proteins are being developed for the therapeutic modulation o f immune inflammation. It is becoming increasingly important to understand the state and involvement of the TNF-alpha /TNFR system in various rheumati c diseases. Tumor necrosis factor-alpha (TNF-alpha) affects its target cells through bi nding to two different receptors, TNFR-p55 and Tumor necrosis factor-alpha (TNF-alpha) affects its target cells through binding to two different recep tors, TNFR-p55 and TNFR-p75. Mitogenic, cytostatic and cytotoxic effects of TNF-alpha on various cells have been reported. In Sjogren'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 i s known about the spatial distribution of TNF-alpha in relation to its rece ptors/target cells in salivary gland tissue. Methods Labial salivary glands (LSG) were obtained from 16 SS patients and 13 healt hy controls and stained using the immunohistochemical peroxidase-anti-perox idase (PAP) method for TNF-alpha, TNFR-p55 and TNFR-p75. Results TNF-alpha, TNFR-p55 and TNFR-p75 staining was absent, weak or relatively in extensive in controls compared to SS patients. Infiltrating mononuclear inf lammatory cells in SS patients displayed moderate to strong TNF-alpha and T NFR expression. In addition, resident vascular endothelial cells, ductal ep ithelial cells and fibroblasts co-expressed TNF-alpha and TNFR. In contrast , acinar end piece cells did not express TNF-alpha or TNFR-p75 although TNF R-p55 was expressed. Conclusion The interrelated localization of TNF receptors and their ligand TNF-alpha i n inflammatory and in endothelial cells suggest a proinflammatory role of T NF-alpha in SS. The expression of TNF-alpha and its receptors in fibroblast s and ductal cells may contribute to ductal hyperplasia and glandular fibro sis. However, in contrast to expectations, the cellular localization of the TNF-alpha /TNRF system argues against its role in acinar cell atrophy.