There is a growing list of pathological situations in which much harm is caused by the effects of TNF. and where blocking of TNF function can be therefore beneficial. One of the current approaches in the attempt to inhibit TNF functioning in disease involves injection of soluble TNF receptors. This approach reproduces a naturally occurring control mechanism. In various inflammatory processes, serum concentrations of the soluble TNF receptors are greatly increased as a result of their proteolytic cleavage triggered by various stimuli associated with inflammatory processes, such as TNF itself. The soluble TNF receptors bind to TNF. They are capable both of competing with the cell surface TNF receptors for TNF and of stabilizing TNF by preventing its spontaneous dissociation into inactive monomers, and thus may affect TNF function in a complex manner. When present in sufficiently high concentrations, however, they act purely as TNF inhibitors.
Ongoing clinical trials with recombinant preparations of soluble receptors, as well as with high molecular weight derivatives of these molecules with lower rates of clearance from the blood circulation (such as soluble receptors fused to the Fab portion of immunoglobulin G (IgG) or linked to polyethyleneglycol), demonstrate their significant therapeutic effects in diseases that involve deleterious action of TNF, including rheumatoid arthritis, the inflammatory bowel diseases, and septic shock.
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