When released into the bloodstream, proinflammatory cytokines have the ability to trigger the transcription of different genes in cells of the blood-brain barrier (BBB), including members of the nuclear factor kappa B (NF-kappaB) family and cyclooxygenase-2 (COX-2), the limiting enzyme for the formation of prostaglandins (PGs). The present study investigated the possibility that interleukin-1beta (IL-1beta) plays an essential role in these events during a systemic inflammatory response. Both wild-type and IL-1beta-deficient mice were killed at different times after two different immunogenic stimuli, i.e., intraperitoneal lipopolysaccharide (LPS) injection and intramuscular turpentine injection, used here as a model of systemic localized inflammatory insult. The inhibitory factor kappaBalpha (IkappaBalpha, index of NF-kappaB activity) and COX-2 transcripts were detected throughout the brain by means of in situ hybridization. Systemic LPS injection caused a strong and rapid expression of IkappaBalpha in endothelial cells lining the BBB of large and small blood vessels and thereafter within parenchymal microglia across the brain. This treatment also provoked a transient expression of COX-2 along cells of the vascular system, and the expression pattern and intensity of the signal for both transcripts were essentially the same in wild-type and IL-1beta-deficient animals. In contrast, the induction of these genes that was quite selective to the cells of the BBB in response to intramuscularly turpentine insult was completely abolished in IL-1beta-deficient mice. Indeed, a late and prolonged expression of IkappaBalpha and COX-2 mRNAs was found along the cerebral blood vessels in response to the sterile and localized inflammation in wild-type mice, whereas such induction was absent in the brain of IL-1beta-deficient animals. These results indicate that IL-1beta has an obligatory role in the activation of NF-kappaB molecules and PGs within endothelial cells of the BBB in an experimental model of intramuscularly turpentine-induced inflammation but not during endotoxemia.