Soluble Cytokine Receptors and Binding Proteins in body fluids: from bench to bedside

In 1989 we coined the notion that soluble cytokine receptors are normal constituents of body fluids. Soluble receptors are circulating proteins corresponding to the extracellular portion of cell-surface receptors. We showed that they might serve as carrier proteins, antagonists or agonists of their corresponding ligands. My approach of combining an enriched source of proteins (500-1000 fold concentrated normal human urine) together with highly specific isolation method, the ligand affinity chromatography, enabled a rapid and efficient isolation of not only soluble receptors corresponding to cell-associated receptors, but also independent binding proteins and associated enzymes. From this list of 11 such proteins, the most prominent ones are the soluble TNF Receptors, the Type I Interferon α/β Receptor and the Interleukin-18 Binding Protein. All contributed to basic research, some were translated into drugs.