RU-486 blocks differentially suppressive effect of stress on in vivo anti-KLH immunoglobulin response.
Exposure to stressors can affect various aspects of immune function, including the antibody response. We have previously reported that rats exposed to an acute session of inescapable tail shock (IS) show long-term reductions in anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) M and IgG and a failure to expand Th1-like cells in response to KLH. To further investigate the potential role of decreased Th1-like cells in the IS-induced reduction of anti-KLH Ig, we examined two isotypes of IgG, IgG1 and IgG2a. Isotype switching is under cytokine control. Interleukin-4 helps B cells switch from making IgM to making IgG1, whereas interferon (IFN)-gamma helps B cells switch from making IgM to making IgG2a. In this paper we report that IS exposure reduces IFN-gamma levels 4 days after exposure to IS+KLH compared with immunized home cage controls. In addition, IS exposure reduced the Th1 cytokine-sensitive anti-KLH IgG2a but not Th2 cytokine-sensitive anti-KLH IgG1. This pattern of isotype reduction suggests that a failure to expand the Th1 cell, which results in less IFN-gamma, may contribute to the the IS-induced reduction in anti-KLH Ig. Glucocorticoids (GCs) differentially regulate Th1 and Th2 cells. Administration of the type II GC receptor antagonist RU-486 before IS blocked the IS-induced suppression in anti-KLH IgM, IgG, and IgG2a. Corticosterone (2.5 mg/kg), however, did not produce the suppression in anti-KLH Ig. These results support a role of corticosterone in mediating IS-induced reductions in in vivo antibody.
Fleshner
M
M
Department of Psychology, University of Colorado-Boulder 80309, USA.
Brennan
F X
FX
Nguyen
K
K
Watkins
L R
LR
Maier
S F
SF
D000276:Adjuvants, Immunologic; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D004597:Electroshock; D006433:Hemocyanins / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000276:immunology*; D013623:Tail
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D015735:Mifepristone; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D003345:Corticosterone