Passage of interleukin-1-beta across the blood-brain barrier is reduced inaged mice: A possible mechanism for diminished fever in aging

Objective: Cytokine signaling is the key to fighting infection. Fever is el icited by the production of inflammatory cytokines, particularly interleuki n-1 beta (IL-1 beta), and the subsequent action of cytokines in the hypotha lamus, In old age, the ability to produce fever in response to infection or to peripheral injections of IL-1 beta is diminished. Intracerebroventricul ar injections of IL-1 beta can still produce a normal fever response in the aged. A logical hypothesis to explain this discrepancy is that passage of IL-1 beta across the blood-brain barrier (BBB) is altered. Method: We used a quantitative in vivo technique, which previously showed a saturable syste m transporting IL-1 beta across the BBB, to investigate the speed at which radiolabeled IL-1 beta crosses from blood to brain in mice of widely differ ent ages. Results: We found that passage of IL-1 beta across the BBB was si gnificantly decreased in old (23-month) mice as compared with young (2-mont h) or middle-aged (12-month) animals. Passage of IL-1 beta across the blood -testis barrier was not significantly different among the groups. The passa ge of radiolabeled albumin across the BBB was not increased in any group, r uling out any disruption of the BBB by IL-1 beta. Conclusion: These results provide a mechanism that could help explain why fever production is reduce d in old age and suggest an important role for the BBB in regulating immune changes. Copyright (C) 2000 S. Karger AG, Basel.