Brain corticotropin-releasing hormone- and interleukin-1 beta-induced suppression of specific antibody production.

Abstract

CRH serves as a central nervous system mediator of autonomic and visceral responses to stress. In addition, central infusion of CRH has a role in the modulation of in vitro correlates of cell-mediated immune function, such as natural killer cell activity and T-lymphocyte proliferation. The present study examined the effects of central CRH on an integrated in vivo immune response, specific antibody production to a novel antigen. Synthetic rat CRH (1.0 micrograms) microinjected into the lateral ventricle significantly (P < 0.001) slowed the induction of a specific immunoglobulin G (IgG) antibody response to the T-cell-dependent antigen keyhole limpet hemocyanin (KLH) after either primary or secondary immunization. CRH-induced suppression of the IgG response in vivo was found after immunization with a low threshold dose of KLH, but not when a 100-fold increased dose of antigen was given. Administration of CRH 20 min before immunization reduced the antibody response, whereas CRH infusion 24 h after KLH exposure failed to alter antibody levels, suggesting that CRH alters initial antigen processing. These effects of CRH on an in vivo antibody response were due to the infusion of CRH into the brain, as a 1.0-micrograms dose of CRH injected either ip or sc had no effect. In addition, central coadministration of the CRH antagonist alpha-helical CRH-(9-41) significantly blocked the immunosuppressive action of CRH. Finally, as central interleukin-1 beta has been reported to modulate cellular immunity, we examined the effect of central infusion of interleukin-1 beta on the KLH antibody response and found that intracerebroventricular interleukin-1 beta (50 ng) produced a significant (P < 0.001) suppression of the IgG response to KLH. These findings extend previous data on central CRH-induced suppression of in vitro measures of cellular immunity and demonstrate that CRH acts in the brain to reduce an in vivo antibody response.