Soluble Receptors for Tumor Necrosis Factor and Neopterin as Parameters of Cell-Mediated Immune Activation

Tumor necrosis factor-α is a pleiotropic cytokine which is capable of inducing numerous immunological and biochemical changes in target cells and tissues, Soluble tumor necrosis factor-α receptors function to modulate the biological properties of tumor necrosis factor-α by enhancing or counteracting its action. In various pathologic states the production and release of soluble tumor necrosis factor receptors may mediate host response and determine the course and outcome of disease by the interaction with tumor necrosis factor-α and competing with cell surface receptors. The actual and forthcoming research of soluble tumor necrosis factor receptors in body fluids such as plasma or serum is a new tool to gain information about immune processes and is providing valuable insight into a variety of pathological conditions. In various diseases concentrations of sTNF-Rs correlate strongly with levels of neopterin, large amounts of which being released from human monocytes/macrophages upon stimulation with interferon-γ. Like neopterin, sTNF-Rs levels show high accuracy in the follow-up and prognosis of various diseases and correlate with the clinical stage and the progression of human immunodeficiency virus infection and sepsis. In cancer and autoimmune diseases, measurement of sTNF-Rs and neopterin provides useful information for monitoring. The quantification of sTNF-Rs and neopterin concentrations often provide even superior information than that obtained with classical disease markers, probably due to the direct involvement of the "interferon-γ/tumor necrosis factor-α system" in the pathogenetic mechanisms of the diseases. Data imply that measurement of sTNF-Rs, especially of the 75kD-type, is a useful adjunct for quantification of the Th-1 type immune response, sharing many characteristics with neopterin.