Sympathectomy-induced immune changes are not abrogated by the glucocorticoid receptor blocker RU-486

Removal of sympathetic noradrenergic input to the immune system by injection of 6-hydroxydopamine (6-OHDA) triggers increases in antigen-specific in vitro splenocyte proliferation and cytokine production in BALB/cJ and C57B1/6J mice. This examines the possible role of glucocorticoids in these previously reported changes. In both strains, chemical sympathectomy triggers an elevation of glucocorticoid levels immediately following injection of 6-OHDA, returning to normal within one to two days. In the BALB/cJ strain, glucocorticoid elevation is seen only after the initial 6-OHDA injection; levels in chronically denervated animals are not different from controls. In the C57B1/6J strain, the increase is seen even with chronically denervated animals. Prior implantation of mice with pellets containing the glucocorticoid receptor antagonist RU-486 does not abrogate denervation-induced increases in cytokine production or proliferation in either strain. In addition to the previously reported increased interleukin (IL)-2 and IL-4 production, there is an increase in IFN-gamma production in the C57B1/6J strain following either acute or chronic denervation. The persistence of denervation-induced changes even when the effect of corticosterone is blocked with RU-486 or diminished with chronic denervation indicates that the changes are driven mainly by a glucocorticoid-independent mechanism.