Relative contributions of peripheral and central sources to levels of IL-1 alpha in the cerebral cortex of mice: assessment with species-specific enzyme immunoassays

The peripheral administration or release of cytokines is associated with central nervous system (CNS) effects that are often due to the actions of cytokines behind the blood-brain barrier (BBB). It is not known whether the majority of cytokine behind the BBB is derived from blood ol is released from the CNS in response to peripheral signals. We addressed this question for interleukin-1 alpha (IL-1 alpha) by infusing human IL-1 alpha (humIL-1 alpha) into mice and measuring humIL-1 alpha and murine IL-1 alpha (murIL-1 alpha) in cerebral cortex and serum with specific, sensitive enzyme immunoassays. In adult mice receiving 50 mu g/kg-24 h of humIL-1 alpha subcutaneously for 48 h, brain and blood samples contained hum-1 alpha but no murIL-1 alpha. This shows that in our study blood-borne IL-1 alpha did not self-stimulate its release in blood or brain. The presence of humIL-1 alpha in brain could only have originated from blood, where it was administered; the brain/blood ratio of 0.126 ml/g indicates that at steady state, brain levels reach about 12% of blood levels. In neonatal mice, both murIL-1 alpha and humIL-1 alpha: were detected in brain and blood after the acute subcutaneous injection of humIL-1 alpha. However, the vast majority of immunoactivity in blood and brain was humIL-1 alpha. These results show that most of the IL-1 alpha appearing in response to circulating IL-I a in areas of the CNS behind the BBB is due to passage across the BBB and not to release from stores endogenous to the CNS. (C) 1997 Elsevier Science B.V.