Interleukin-6 is secreted from the brain after
intracerebroventricular injection of interleukin i[beta] in the
rat.
Romero, Luz I., Ildik[grave]o Kakucska, Ronald M. Lechan, and Seymour
Reichlin.
Division of Endocrinology, Metabolism, Diabetes and Molecular
Medicine, Department of Medicine, Tufts University School of Medicine
and New England Medical Center.
APStracts 2:0300R, 1995.
To test the hypothesis that the brain is a source of the IL-6 that
appears in the peripheral circulation of the rat after
intracerebroventricular (icv) injection of IL-1[beta], the
concentration of bioactive IL-6 in superior sagital sinus (SSS) blood
plasma was compared to aortic plasma 4 hr after icv injection of 100
ng of recombinant human IL-1[beta] at a time at which cerebrospinal
fluid (CSF) IL-6 concentration was found to be markedly elevated. In
three separate experiments CSF IL-6 concentration was significantly
elevated after icv IL-1[beta] as compared with saline control
injections (25,879 +/- 11,472 vs 35.5 +/- 5; 32,323 +/- 4,945 vs. 128
+/- 29; 114,410 +/- 33,563 vs. 848 +/- 250 pg/ml +/- SE
respectively). The concentration of plasma IL-6 (pg/ml) in the aorta
of rats injected icv with IL-1 was greater than in controls (252 +/-
93 vs 36.7 +/- 8.3, p=0.0037; 361 +/- 95 vs 57 +/- 13, p=0.02; 2,254
+/- 550 vs 1,239 +/- 666, p=0.26, (n.s.). In IL-1 injected animals,
superior sagital sinus (SSS) venous plasma IL-6 (pg/ml +/- SE) was
greater than in the aorta in all three studies (1,617 +/- 357 vs 252
+/- 93, p=0.0011; 3,754 +/- 1,188 vs 361 +/- 95, p=0.024; 8208 +/-
1,388 vs 2,254 +/- 550, p=0.0054). The concentration difference
(pg/ml +/- SE) between SSS and aorta was significantly greater after
IL-1[beta] injection than in diluent injected animals (1,365 +/- 369
vs 48.3 +/- 13, p=0.0083; 3,393 +/- 1,203 vs 126 +/- 59, p=0.035;
5954 +/- 1,260 vs 494 +/- 774, p=0.0042). Suppression of peripheral
sympathetic activation by pre-ganglionic cholinergic blockade
(chlorisondamine, 250 [mu]g sc) did not prevent the usual IL-1
-induced elevation in aortic blood IL-6 (3,272 +/- 1,174 vs. 244 +/-
74 pg/ml +/- SE, p=0.0012 ), nor the in creased SSS-aortic gradient
(2,541 +/- 1,134 vs 165 +/- 48, p=0.0142 by Mann-Whitney comparison).
Injection of rat/human CRH (10.0 [mu]g) icv did not change IL-6
concentration in CSF or in peripheral blood. These studies
demonstrated that the brain and/or its supporting structures are
activated by intracerebroventricular IL-1[beta] to release IL-6 into
the blood, and that the effect is not dependent upon peripheral
sympathetic activity or central mobilization of CRH. Direct secretion
of IL-6 and possibly of other cytokines from the brain is postulated
to be a pathway of neuroimmunmodulation.
Received 21 April 1994; accepted in final form 17 August 1995.
APS Manuscript Number R208-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95