Proposed mechanisms by which peripheral cytokines activate CRH-producing neurons of the PVN in the hypothalamus (rat brain). ACTH, adrenocorticotropic hormone; AP, area postrema; CRH, corticotropin-releasing hormone; HIPP, hippocampus; ME, median eminence; NE, norepenephrine; NO, nitric oxide; NTS, nucleus tractus solitarius; OVLT, organum vascularis of lateral terminalis; PG, prostaglandins; PVN, paraventricular nucleus of the hypothalamus. ★ = site of entry of peripheral cytokine signals. Reprinted by permission from Silverman et al. (274).