RECOMBINANT HUMAN INTERLEUKIN-1-ALPHA DILATES PIAL ARTERIOLES AND INCREASES CEREBROSPINAL-FLUID PROSTANOIDS IN PIGLETS

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 (35%) 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.