Catecholamines increase monocyte tnf receptors and inhibit tnf
through [beta]2 adrenoreceptor activation.
Guirao, Xavier, Ashwini Kumar, Joshua Katz, Michelle Smith, Edward
Lin, Chris Keogh, Steve E. Calvano, and Stephen F. Lowry.
Laboratory of Surgical Metabolism, Department of Surgery, New York
Hospital Cornell Medical Center. New York, NY 10021, and Division of
Surgical Sciences, University of Medicine and Dentristry of New
Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ
08901.
APStracts 4:0203E, 1997.
Post-injury deficits in monocyte TNF receptors (moTNFR) activity may
alter beneficial functions during an inflammatory response. Several
counter-regulatory hormones elicited during inflammation may modulate
TNF activity, but little is known about their influence on moTNFR.
Also, catecholamines inhibit TNF production but the adrenoreceptor
mechanism of this effect has not been fully clarified. To determine
the effect of catecholamines and corticosteroids on moTNFR, whole
blood was co-incubated for up to 8 (moTNFR) or 24h (cytokines) in the
presence of lipopolysaccharide (LPS 100 ng/ml) and 1) epinephrine
(EPI, 10-6 M), dexamethasone (DX, 10-6 M) or both (EPIDX, 10-6 M) to
asses the expression of total-moTNFR, moTNFR-I and moTNFR-II. 2) EPI
and norepinephrine (EPINOR, 10-6 M ) and the [alpha]1+2, [beta]1+2,
[beta]1 or [beta]2 adrenergic antagonists were utilized to asses the
role of such adrenoreceptors on total-moTNFR and TNF production, and
dibutyryl cAMP (dbt cAMP) alone or in combination with the
phosphodiesterase inhibitor RO-20-1724-000, to study the cAMP
dependent pathway on total-moTNFR. We found that EPI upregulated
total-moTNFR and moTNFR-II. DX did not significantly influence total
-moTNFR nor moTNFR-II. Also EPINOR increased total-moTNFR and
inhibited TNF by a [beta]2 dependent mechanism. Dbt cAMP (10-5 M)
modestly enhanced total-moTNFR. This suggests a common mechanism for
acutely enhancing moTNFR and attenuation of soluble TNF appearance
during conditions of severe stress.
Received 24 March 1997; accepted in final form 17 September 1997.
APS Manuscript Number E134-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997