Interleukin-1b peptides induce cerebral pial arteriolar dilation in
anesthetized newborn pigs.
Shibata, Masaaki, Helena Parfenova, Samuel L. Zuckerman, Jerome M.
Seyer, James M. Krueger, and Charles W. Leffler.
Laboratory for Research in Neonatal Physiology, aDepartment of
Physiology and Biophysics, University of Tennessee, Memphis, TN
38163; Division of Critical Care Medicine, St. Jude Children's
Research Hospital, Memphis, TN 38101; and cVeterans Administration
Medical Center, Memphis, TN 38163, U. S. A.
APStracts 2:0330R, 1995.
Inflammatory cytokines may affect cerebral circulation under
pathological conditions. Responses of cerebral pial arterioles to one
such cytokine, interleukin-1b (IL-1b) and its inhibitor (soluble IL-1
receptor, sIL-1R) were examined in anesthetized newborn pigs using
closed cranial windows. Levels of prostanoids and cyclic nucleotides
in periarachnoid cerebral spinal fluid (CSF) were measured. To
examine the structure-activity relationship of the parent IL-1b
molecule, two IL-1b fragments with amino acid sequences of 187-204
(IL-1b187-204) and 208-240 (IL-1b208-240) were tested for their
effects on pial arterioles. Diameter changes of pial arterioles were
sequentially recorded every 5 min for 30 min after topical
application of IL-1 peptides. CSF was sampled at the end of the 30
min. IL-1b dose-dependently induced arteriolar dilation and increased
prostaglandin E2 (PGE2), 6-keto-PGF1a, cyclic AMP (cAMP), and cyclic
GMP (cGMP). Intravenous indomethacin blocked the IL-1b-induced
vasodilation, the increased prostanoids, and the increased cAMP, but
not the increased cGMP. Neither heat-inactivated IL-1b nor IL-1b
vehicle affected arteriolar diameter or CSF levels of prostanoids.
The sIL-1R blocked the IL-1b-induced vasodilation and the increased
CSF prostanoids. IL-1b208-240 also induced pial arteriolar dilation;
however, its vasodilatory potency was 1,000 times less than that of
the whole IL-1b molecule. IL-1b187-204 did not induce pial arteriolar
dilation even when its dose was increased to the level of IL-1b208
-240. These results suggest that IL-1b, through the activation of
membrane-bound IL-1b receptors, induces pial arteriolar dilation via
mechanisms that involve prostanoids and cyclic nucleotides. The
results also indicate that the 208-240 amino acid sequence of IL-1b
has a sequence specific physiological function.
Received 14 July 1995; accepted in final form 15 November 1995.
APS Manuscript Number R441-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95