Involvement of Brain Cytokines in Stress-induced Immunosuppression

In the brain-immune system interactions, cytokines produced in the periphery and the brain during inflammatory and noninflammatory stress play an important role as signal molecules. The central administration of interleukin-1β (IL-1β) and interferon-α (IFN-α) is shown to suppress the splenic natural killer (NK) cell activity in rats, which is mediated by, at least in part, the sympathetic innervation to the spleen. The central IL-1β and IFN-α increase the splenic sympathetic nerve activity, and an electrical stimulation of the nerve results in a suppression of splenic NK cell activity through a β-adrenergic receptor-mediated process. Furthermore, the findings that (1) immobilization (IMB) stress produced an elevation of extracellular concentration of noradrenaline in the spleen, (2) the IMB-induced reduction of splenic NK activity was partially blocked by splenic denervation, (3) pretreatment with central injection of neutralizing anti-IL-1β antibody attenuated the IMB-induced NK suppression, and (4) hypothalamic IL-1β and IFN-α mRNA were increased after 1 h IMB suggested that IL-1β and IFN-α produced in the brain may be key substances mediating the IMB stress-induced immunosuppression.