Recombinant human interleukin 1 alpha dilates pial arterioles and increases cerebrospinal fluid prostanoids in piglets
Shibata, M.; Leffler, C.W.; Busija, D.W.
American Journal of Physiology 259(5 Pt 2): H1486-H1491
1990
ISSN/ISBN: 0002-9513 PMID: 2240247 Document Number: 363150
Effects of recombinant human interleukin 1.alpha. (IL-1.alpha.) on vasomotor tone of pial arterioles and cerebrospinal fluid (CSF) prostanoid levels were examined in anesthetized piglets by employing the closed cranial window method. IL-1.alpha. in a dose of 10.8 .mu.g infused under the window increased pial arteriolar diameter [initial size, 160 .+-. 9 (SE) .mu.m] significantly at 15 min postinfusion through 30 min (30-min study), exhibiting a maximum dilation of 13 .+-. 1% (n = 8) over the control levels. Significant increases in levels of prostaglandin E2 (PGE2, 75%), 6-keto-PGF1.alpha. (84%), and PGF2.alpha. (25%) but not for thromboxane B2 (TxB2 2%) were observed when CSF was sampled from under the window 30 min after 10.8 .mu.g IL-1.alpha. A lower dose of IL-1.alpha. (1.0 .mu.g, n = 4) significantly increased the diameter of pial arterioles with a tendency for longer onset (25-30 min) and smaller magnitude (9-10%) than the higher dose. In IL-1.alpha. time-response studies, CSF sampled 10 min after 10.8 .mu.g IL-1.alpha. infusion (10-min study, n = 6) under the window exhibited the same levels of PGE2, 6-keto-PGF1.alpha., PGF2.alpha., and TxB2 as those of the controls. There was no vasodilation in the 10-min study. However, when sampled 20 min after 10.8 .mu.g IL-1.alpha. (20-min study, n = 6), CSF levels of all prostanoids except for TxB2 significantly increased over the controls. Arteriolar diameter also increased in the 20-min study to a level almost equal to that observed in the 30-min study with the same dose. When these responses were tested in animals pretreated with indomethacin, enhanced prostanoid synthesis was blocked and arteriolar dilation did not occur (n = 9). Heat-denatured IL-1.alpha. (n = 4) increased neither arteriolar diameter nor CSF prostanoid levels in the 30-min study. These results suggest that IL-1.alpha. dilates pial arterioles via a mechanism involving prostanoids.