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.
Kruszewska
B
B
Center for Psychoneuroimmunology Research, University of Rochester Medical Center, Rochester, New York, 14642, USA. Barbara_Kruszewska@urmc.rochester.edu
Felten
D L
DL
Stevens
S Y
SY
Moynihan
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D006433:Hemocyanins / Q000276:immunology; D006727:Hormone Antagonists / Q000494:pharmacology*; D007107:Immune System / Q000737:chemistry* / Q000187:drug effects* / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000276:immunology; D013154:Spleen / Q000737:chemistry / Q000276:immunology; D013562:Sympathectomy; D013565:Sympatholytics; D013566:Sympathomimetics / Q000032:analysis
D006727:Hormone Antagonists; D007376:Interleukin-2; D011965:Receptors, Glucocorticoid; D013565:Sympatholytics; D013566:Sympathomimetics; D015847:Interleukin-4; D015735:Mifepristone; D007371:Interferon-gamma; D016627:Oxidopamine; D006433:Hemocyanins; D003345:Corticosterone; D009638:Norepinephrine