The induction of IL-1β by stress in the periphery and the brain, and the reciprocal interactions between these systems (Fig. 3) (Dobbin et al., 1991; Nguyen et al., 1998) raises the question as to whether peripheral blockade of IL-1β is sufficient to block the neuronal and behavioral effects of chronic stress. The blood brain barrier (BBB) protects the brain from systemic pathogens, as well as the entry of peripheral peptides and proteins. Inflammatory cytokines, including IL-1β, are large polypeptides and are thus unlikely to cross the BBB (Watkins et al., 1995). However, there are several mechanisms by which the brain and peripheral systems can communicate. The vagus nerve, a cranial nerve connecting the brain to the periphery, has an afferent fiber by which peripheral stimulation can be directly conducted to the central nervous system (Maier et al., 1998). In support of this, vagotomy has been reported to block numerous brain-mediated sickness responses following both LPS and IL-1β administration (Maier et al., 1998; Nguyen et al., 1998; Watkins et al., 1995).
