TNF -RII (80kDa) ELISA

Tumor Necrosis Factor (TNF)

was originally discovered in sera of animals and was found to cause hemorrhagic necrosis of some transplantable mouse and human tumors and to exhibit primarily cytotoxic activities against tumor but not normal cells in vitro. The TNF family consists of two proteins designated TNF-alpha, also called cachectin, and TNF-beta, also called lymphotoxin, which are pleiotropic cytokines that can mediate a wide variety of biological effects.

Both TNF-alpha and TNF-beta have been shown to interact with a cell through specific high affinity receptors with a few hundred up to more than 20,000 copies per cell. TNF-receptors have been demonstrated on a wide variety of human somatic cells including fibroblasts, endothelial cells, adipocytes, liver membranes, granulocytes and several tumor cell lines. Normal and malignant human myeloid cells as well as mitogen-stimulated lymphocytes express similar numbers of TNF receptors (400 - 1,900 per cell), whereas resting lymphoid cells have fewer, red blood cells and platelets have no detectable TNF receptors. In most cases no correlation is observed between receptor number and sensitivity to TNF. Based on gel filtration experiments the receptor appears to be a complex of different proteins with a molecular weight of 350 kDa. In a variety of cell lines two different types of TNF receptors with 75-80 and 55-60 kDa respectively have been identified. The present assay provides a simple, rapid and highly sensitive method for the determination of soluble TNF-R (80 kDa) levels in body fluids or cell culture supernatants. This assay will help to clarify the possible diagnostic and prognostic value of circulating sTNF-R (80 kDa) in various neoplastic and inflammatory diseases.

• autoimmune diseases:
  in patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS), plasma concentrations of both types of TNF receptors and in mixed connective tissues disease (MCTD) patients, type TNF-R (80 kDa) receptors are significantly elevated compared to controls. In rheumatoid arthritis patients, concentrations of TNF-R (60 kDa) and TNF-R (80 kDa) are significantly higher than in controls.
• hematology:
  upregulation of TNF-R is found in reactive hyperplasia. Expression of TNF-R is mainly seen in high-grade malignant Non-Hodgkin`s lymphoma. Concentrations of the 60 kDa type sTNF-R are significantly higher in Hodgkin´s Disease patients than in healthy controls.
• HIV:
  sTNF-R is upregulated following seroconversion, remains persistently high during the asymptomatic phase and becomes even more elevated in some ARC and AIDS patients.
• kidney:
  sTNF-R is elevated in serum and urine of patients on chronic hemodialysis. This may have beneficial effects on inflammatory conditions.
• liver:
  differential diagnosis of ascites: sTNF-R levels in ascites are significantly elevated in patients with malignancy-related and infected ascites compared with patients with uncomplicated hepatic ascites.
• Malaria:
  the excessive release of TNF induced by malaria parasites is controlled by sTNF-R that binds and deactivates TNF.
• ovary:
  elevated levels of sTNF-R inhibit the cytolytic activity of recombinant TNF given in the course of immunotherapy.
• pancreas:
  human pancreatic carcinoma cells express receptors for TNF. Elevated sTNF-R levels may therefore be of prognostic value for detection of pancreatic carcinoma. (31)
• pregnancy:
  sTNF-R levels are a physiologic constituent of amniotic fluid (AF). Elevations of sTNF-R levels in AF are directly related to intrauterine infection and preterm parturition.
• skin:
  sTNF-R is significantly elevated in patients with severe burns.
• therapy:
  recombinant TNF as a cancer therapeutic can provoke release of sTNF-R.