SYMPATHECTOMY-INDUCED IMMUNE CHANGES ARE NOT ABROGATED BY THE GLUCOCORTICOID RECEPTOR BLOCKER RU-486

Removal of sympathetic noradrenergic input to the immune system by inj ection of 6-hydroxydopamine (6-OHDA) triggers increases in antigen-spe cific in vitro splenocyte proliferation and cytokine production in BAL B/cJ and C57B1/6J mice. This examines the possible role of glucocortic oids in these previously reported changes. In both strains, chemical s ympathectomy triggers an elevation of glucocorticoid levels immediatel y following injection of 6-OHDA, returning to normal within one to two days. In the BALB/cJ strain, glucocorticoid elevation is seen only af ter the initial 6-OHDA injection; levels in chronically denervated ani mals are not different from controls. In the C57B1/6J strain, the incr ease is seen even with chronically denervated animals. Prior implantat ion of mice with pellets containing the,glucocorticoid receptor antago nist RU-486 does not abrogate denervation-induced increases in cytokin e production or proliferation in either strain. In addition to the pre viously reported increased interleukin (IL)-2 and IL-4 production, the re is an increase in IFN-gamma production in the C57B1/6J strain follo wing either acute or chronic denervation. The persistence of denervati on-induced changes even when the effect of corticosterone is blocked w ith RU-486 or diminished with chronic denervation indicates that the c hanges are driven mainly by a glucocorticoid-independent mechanism. (C ) 1998 Academic Press.