Biological significance of soluble IL‐2 receptor

Abstract

A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC) activation and interleukin-2 receptor (IL-2R) expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R) is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting findings are discussed in the light of the data showing that sIL-2R production correlates with IL-2 production.

Plasma Concentrations of Interleukin-1β, Interleukin-6, Soluble Interleukin-2 Receptor and Tumor Necrosis Factor α of Depressed Patients in Japan

“…One of the most interesting results we found was that sIL-2R was positively correlated with POMS-T-A and tended to be correlated with HAM-D. Other reports suggest the increased concentration of sIL-2R in the blood of depressed patients [7,18]. Soluble IL-2R is known to be released from activated T lymphocytes into the blood, and its release appears to be associated with IL-2 secretion in various pathological phenomena [19]. Because IL-2 is one of the most potent cytokines which contribute to the stressinduced activation of hypothalamus-pituitary-adrenal axis [20], the present finding of the relationship between sIL-2R and mood may reflect the stressful state in depressed patients.…”

Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia on long-term treatment with antipsychotics

“…1 The correlation between the number of cigarettes smoked and negative symptom or IL-2 in schizophrenia and IL-6 levels with IL-2 levels reduced in direct proportion to greater cigarette consumption (Sopori 2002;Mamata et al 2005;Friedman et al 2006). IL-2 is a T cell growth factor, which is produced by activated T cells and plays an important role in T cell and B cell activation and proliferation (Caruso et al 1993). IL-6, a 26-kDa protein, is released from peripheral immune cells of the monocyte/ macrophage lineage and acts as a mediator of peripheral acute-phase inflammatory responses (Maes et al 1994).…”

Elevation of proinflammatory cytokines in patients with Aicardi-Goutières syndrome

“…Certain cytokines are of particular interest for possible plasma monitoring. These include Flt3, a dendritic cell maturation marker 14 ; IP-10, known to be increased in plasma in autoimmune disorders such as neuropsychiatric lupus and persistently elevated in plasma; sIL-2ra, associated with B-and T-cell activation and used as a monitoring tool in a number of autoimmune, [15][16][17] infectious, 18 and oncologic 19 disorders; and TNFa, a proinflammatory cytokine with widespread effects.…”