Systemic cytokine administration can affect blood-brain barrier permeability in the rat.
The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium.
Saija
A
A
Dep. Farmaco-Biologico, Sch. Pharmacy, University of Messina, Italy.
Princi
P
P
Lanza
M
M
Scalese
M
M
Aramnejad
E
E
De Sarro
A
A
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001810:Blood Volume; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D002250:Carbon Radioisotopes; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D002250:Carbon Radioisotopes; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C100049:2-aminoisobutyric acid