Inflammatory reactions against invaders in the body call upon cytokine molecules that elicit systemic responses, such as fever, fatigue, increased pain sensitivity and appetite loss, mediated by the central nervous system. But how cytokines can induce these effects has been a mystery as they are unlikely to cross the blood–brain barrier^,,. Here we show that cerebral vascular cells express components enabling a blood-borne cytokine to stimulate the production of prostaglandin E₂, an inflammatory mediator whose small size and lipophilic properties allow it to diffuse into the brain parenchyma. As receptors for this prostaglandin are found on responsive deep neural structures^,,, we propose that the activated immune system controls central reactions to peripheral inflammation through a prostaglandin-dependent, cytokine-mediated pathway.