Differences between cytokines effects in the microcirculation of
the rat.
Baudry, Nathalie, Christine Rasetti, and Eric Vicaut.
Laboratoire d'[acute]etude de la microcirculation. Dept. de
Biophysique. Hopital F. Widal. 200 rue du Fg. St-Denis 75010 Paris,
France.
APStracts 3:0177H, 1996.
We studied by in vivo microscopy in rat cremaster muscle the acute and
delayed effects of short exposure to the tumor necrosis factor (TNF),
interleukin-1[beta] (IL-1[beta]), and interleukin-6 (IL-6) on basal
tone and vascular reactivity of second- to fourth-order arterioles
(A2 to A4). A twenty-minute exposure to rTNF (0.1 to 10?ng/ml)
induced a significant arteriolar vasodilation but no significant
changes in basal tone were found after exposure to the same doses of
IL-1[beta]. In contrast, the same exposure to IL-6 (0.1 to 10?ng/ml)
induced a significant dose-dependent vasoconstriction (i.e. 8, 15 and
21 % at 10?ng/ml in A2 to A4 arterioles respectively). This
vasoconstriction was inhibited by the thromboxane A2 receptor
antagonist SQ 29548. We did not find any significant effect of rTNF
or IL-6 or vascular reactivity to norepinephrine immediately after
exposure to these two cytokines or one hundred?minutes after the end
of the exposure. Contrastingly, a large dose-dependent decrease in
reactivity to norepinephrine (NE) was found immediately after
exposure to IL-1[beta] and still persisted one hundred?minutes after
the end of the exposure. Such a decrease was not found for the
vasoconstriction in response to KCl. We conclude that at the
microvascular level large differences exist between the three
cytokines generally considered to mediate the harmful cardiovascular
effects in sepsis. 1/TNF but not IL-1[beta] is responsible for a
vasodilatory effect whereas the effect of IL-6 is a thromboxane-A2
mediated vasoconstriction. 2/ Short exposure to IL-1[beta] but not to
rTNF or IL-6 diminishes the response of the arterioles to
norepinephrine but not to KCl.
Received 8 March 1996; accepted in final form 15 April 1996.
APS Manuscript Number H229-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96