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, i ncluding the antibody response. We have previously reported that rats exposed to an acute session of inescapable tail shock (IS) show long-t erm reductions in anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) M and IgG and a failure to expand Th1-like cells in response to K LH. To further investigate the potential role of decreased Th1-like ce lls in the IS-induced reduction of anti-KLH Ig, we examined two isotyp es of IgG, IgG1 and IgG2a. Isotype switching is under cytokine control . Interleukin-4 helps B cells switch from making IgM to making IgG1, w hereas interferon (IFN)-gamma helps B cells switch from making IgM. to making IgG2a. In this paper we report that IS exposure reduces IFN-ga mma levels 4 days after exposure to IS + KLH compared with immunized h ome cage controls. In addition, IS exposure reduced the Th1 cytokine-s ensitive anti-KLH IgG2a but not Th2 cytokine-sensitive anti-KLH IgG1. This pattern of isotype reduction suggests that a failure to expand th e Th1 cell, which results in less IFN-gamma, may contribute to the the IS-induced reduction in anti-KLH Ig. Glucocorticoids (GCs) differenti ally regulate Th1 and Th2 cells. Administration of the type II GC rece ptor antagonist RU-486 before IS blocked the IS-induced suppression in anti-KLH IgM, IgG, and IgG2a. Corticosterone (2.5 mg/kg), however, di d not produce the suppression in anti-KLH Ig. These results support a role of corticosterone in mediating IS-induced reductions in in vivo a ntibody.