Tumour necrosis factor (TNF) binding proteins (soluble TNF receptor forms) with possible roles in inflammation and...

Inhibitors of Tumour Necrosis Factor (TNF) may be necessary for protection of the host against harmful systemic manifestations of this cytokine such as in the septic syndrome and inflammatory conditions. TNF-binding proteins (TNF-BP) have been identified and shown to be the soluble extracellular domains of two transmembrane TNF receptors produced by proteolytic cleavage. TNF-BP inactivates TNF by formation of high affinity complexes thereby reducing the binding of TNF to target cell membrane receptors. In addition, TNF is stabilized in complex with TNF-BP, and under certain conditions the complex may act as a slow releaser of biologically active TNF. TNF can induce the release of TNF-BP in vivo which might neutralize the bioactivity of TNF. Cytokine control by natural and recombinant cytokine inhibitors such as TNF-BP could be a promising therapeutic approach in chronic inflammatory disorders to shift the balance between a cytokine-induced response and counteracting "anticytokines". A local production of TNF-BP in some tumour tissues may inactivate TNF for the benefit of the tumour. In some leukemias e.g. B-cell chronic lymphocytic leukemia, where TNF can act as a growth factor for the malignant cells, TNF-BP may be growth inhibitory.