Soluble Cytokine Receptor Subunits Modulate Catecholaminergic Cell Activity

Soluble cytokine receptors (SCR) modulate cytokine signaling and are increased in states of abnormal immune activation. SCR’s are also increased in psychiatric and neurological disorders associated with altered brain catecholaminergic activity; although, there is no evidence that any soluble cytokine receptor alone modulates such activity. One such soluble cytokine, soluble IL-2 receptor (sIL-2R) modulates lymphocyte activity. Here, we discovered that soluble IL-2 receptors (sIL-2Rα, sIL-2Rβ) dose-dependently increase cAMP levels in differentiated PC12 cells. sIL-2Rγ and sIL-6Rα have produced no effect. Co-treatment of sIL-2Rs with IL-2 alters cAMP levels in a concentration-dependent manner. This is the first evidence that soluble receptors modulate catecholaminergic cell activity. Thus, soluble cytokine receptors, including the α and β subunits, may represent new therapeutic targets for relevant psychiatric and neurological disorders.