Soluble cytokine receptors: basic immunology and clinical applications

Abstract

Cytokine activity is tightly regulated at multiple levels. Soluble cytokine receptors (sCR) contribute to the regulation of cytokine activity by modulating the ability of cytokines to bind their membrane receptors and generating a response. Endogenous sCR are generated by proteolytic cleavage or "shedding" of the membrane receptor and/or by translation from alternatively spliced messages different from those encoding the membrane forms. The resulting soluble receptors retain their ligand-binding ability and with some exceptions act as competitive inhibitors of the binding and biologic activity of their ligand, both in vitro and in vivo. However, sCR can also have certain effects on cytokines, such as structural stabilization, protection from proteolysis, and prolonged in vivo half-life, which are consistent with an added role as carrier proteins, and which may under some conditions result in potentiation of cytokine activity in vivo. The exact contribution of endogenous sCR to the regulation of immune or inflammatory responses has not yet been established unequivocally. Nonetheless, evidence indicates that the levels of certain sCR in serum and biological fluids correlate with immunological activation and/or disease activity in a variety of clinical conditions. Hence, sCR levels may have significant value as markers in disease management and prognosis. Moreover, sCR have also shown promising potential as immunotherapeutic agents for a variety of clinical disorders, including sepsis, inflammation, and autoimmune and malignant diseases.