Passage of interleukin-1-beta across the blood-brain barrier is reduced in aged mice: a possible mechanism for diminished fever in aging.
OBJECTIVE
Cytokine signaling is the key to fighting infection. Fever is elicited by the production of inflammatory cytokines, particularly interleukin-1beta (IL-1beta), and the subsequent action of cytokines in the hypothalamus. In old age, the ability to produce fever in response to infection or to peripheral injections of IL-1beta is diminished. Intracerebroventricular injections of IL-1beta can still produce a normal fever response in the aged. A logical hypothesis to explain this discrepancy is that passage of IL-1beta across the blood-brain barrier (BBB) is altered.


METHODS
We used a quantitative in vivo technique, which previously showed a saturable system transporting IL-1beta across the BBB, to investigate the speed at which radiolabeled IL-1beta crosses from blood to brain in mice of widely different ages.


RESULTS
We found that passage of IL-1beta across the BBB was significantly decreased in old (23-month) mice as compared with young (2-month) or middle-aged (12-month) animals. Passage of IL-1beta across the blood-testis barrier was not significantly different among the groups. The passage of radiolabeled albumin across the BBB was not increased in any group, ruling out any disruption of the BBB by IL-1beta.


CONCLUSIONS
These results provide a mechanism that could help explain why fever production is reduced in old age and suggest an important role for the BBB in regulating immune changes.
McLay
R N
RN
Tulane University School of Medicine and VA Medical Center, New Orleans, LA 70112-1262, USA.
Kastin
A J
AJ
Zadina
J E
JE
D000375:Aging / Q000276:immunology*; D000818:Animals; D001693:Biological Transport, Active / Q000276:immunology / Q000502:physiology; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000502:physiology; D005334:Fever / Q000276:immunology* / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D007375:Interleukin-1