|
|
 Previous Article | Table of Contents | Next Article 
Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1
receptor antagonist inhibits IL-1-induced cytokine synthesis and blocks the
binding of IL-1 to its type II receptor on human monocytes
EV Granowitz, BD Clark, E Vannier, MV Callahan and CA Dinarello
Department of Medicine, New England Medical Center Hospitals, Boston, MA.
Interleukin-1 (IL-1) induces IL-1, tumor necrosis factor alpha (TNF alpha),
and IL-6 gene expression and synthesis in a variety of cells. In this
study, we investigated the ability of human recombinant IL-1 receptor
antagonist (IL-1ra) to inhibit IL-1-induced cytokine production in human
peripheral blood mononuclear cells (PBMC) and isolated monocytes. IL-1ra
alone at concentrations as high as 1 microgram/mL did not induce IL-1
alpha, IL-1 beta, TNF alpha, or IL-6 synthesis. Suppression of IL-1-induced
IL-1, TNF alpha, or IL-6 synthesis was dose-dependent (P less than or equal
to .0001). At a twofold molar excess, IL-1ra inhibited IL-1-induced IL-1 or
TNF alpha synthesis by 50% (P less than .01); an equimolar concentration of
IL- 1ra inhibited synthesis of these two cytokines by over 20% (P less than
.05). A 10-fold molar excess of IL-1ra over IL-1 beta reduced IL-1 beta-
induced IL-1 alpha by 95% (P = .01) and IL-1 alpha-induced IL-1 beta by 73%
(P less than .01). IL-1ra added to PBMC 8 hours after stimulation with IL-1
beta was still able to inhibit IL-1 alpha, TNF alpha, and IL- 6 synthesis
(P less than or equal to .01). A similar reduction in IL-1 beta-induced
IL-1 alpha was observed when IL-1 beta was removed from the cultures after
8 hours of stimulation (P less than .05), suggesting a prolonged presence
of IL-1 or restimulation of IL-1 receptors on monocytes is required for the
induction of cytokines. In elutriated monocytes, a 10-fold molar excess of
IL-1ra reduced IL-1 beta-induced IL-1 alpha by 82% (P less than .05), TNF
alpha by 64% (P = .05), and IL- 6 by 47% (P less than .05). 125I-IL-1 beta
was bound to purified monocytes, cross-linked, and immunoprecipitated.
Sodium dodecyl sulfate- polyacrylamide gel electrophoresis showed a band at
85 Kd corresponding to the 68-Kd IL-1 receptor type II (IL-1RtII). Excess
unlabeled IL-1 beta or IL-1ra blocked the binding of 125I-IL-1 beta to the
IL-1RtII. We conclude that IL-1ra inhibits IL-1-induced cytokine synthesis
and competes with IL-1 for the IL-1RtII on human monocytes.
Volume 79,
Issue 9,
pp. 2356-2363,
05/01/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Ganaiem, M. AbuElhija, E. Lunenfeld, N. Cherniy, N. Weisze, S. B.-S. Itach, H. Breitbart, R. Apte, and M. Huleihel
Effect of Interleukin-1 Receptor Antagonist Gene Deletion on Male Mouse Fertility
Endocrinology,
January 1, 2009;
150(1):
295 - 303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Harris, A. Fasano, and D. L. Mann
Cutting Edge: IL-1 Controls the IL-23 Response Induced by Gliadin, the Etiologic Agent in Celiac Disease
J. Immunol.,
October 1, 2008;
181(7):
4457 - 4460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Simitsopoulou, E. Roilides, J. Dotis, M. Dalakiouridou, F. Dudkova, E. Andreadou, and T. J. Walsh
Differential Expression of Cytokines and Chemokines in Human Monocytes Induced by Lipid Formulations of Amphotericin B
Antimicrob. Agents Chemother.,
April 1, 2005;
49(4):
1397 - 1403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. M. Irikura, M. Lagraoui, and D. Hirsh
The Epistatic Interrelationships of IL-1, IL-1 Receptor Antagonist, and the Type I IL-1 Receptor
J. Immunol.,
July 1, 2002;
169(1):
393 - 398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Calkins, D. D. Bensard, B. D. Shames, E. J. Pulido, E. Abraham, N. Fernandez, Xianzhong Meng, C. A. Dinarello, and R. C. McIntyre JR
IL-1 regulates in vivo C--X--C chemokine induction and neutrophil sequestration following endotoxemia
Innate Immunity,
February 1, 2002;
8(1):
59 - 67.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. K. Furse, R. G. Rossetti, and R. B. Zurier
Gammalinolenic Acid, an Unsaturated Fatty Acid with Anti-Inflammatory Properties, Blocks Amplification of IL-1{{beta}} Production by Human Monocytes
J. Immunol.,
July 1, 2001;
167(1):
490 - 496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. C. Higgins, Y. Wu, and A. E. Postlethwaite
Intracellular IL-1 Receptor Antagonist Is Elevated in Human Dermal Fibroblasts That Overexpress Intracellular Precursor IL-1{alpha}
J. Immunol.,
October 1, 1999;
163(7):
3969 - 3975.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Del Rey, I. Klusman, and H. O. Besedovsky
Cytokines mediate protective stimulation of glucocorticoid output during autoimmunity: involvement of IL-1
Am J Physiol Regulatory Integrative Comp Physiol,
October 1, 1998;
275(4):
R1146 - R1151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Rasmussen, M. Diamant, M. Blichert-Toft, K. Bendtzen, and U. Feldt-Rasmussen
The Effects of Interleukin-1{beta} (IL-1{beta}) on Human Thyrocyte Functions Are Counteracted by the IL-1 Receptor Antagonist
Endocrinology,
May 1, 1997;
138(5):
2043 - 2048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. I. Hulkower, E. R. Otis, J. Li, B. W. Ennis, D. J. Cugier, R. L. Bell, G. W. Carter, and K. B. Glaser
Induction of Prostaglandin H Synthase-2 and Tumor Necrosis Factor-alpha in Human Amnionic WISH Cells by Various Stimuli Occurs Through Distinct Intracellular Mechanisms
J. Pharmacol. Exp. Ther.,
February 1, 1997;
280(2):
1065 - 1074.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. D. Acton, P. S. Dahlberg, M. E. Uknis, H. G. Klaerner, G. S. Fink, J. G. Norman, and D. L. Dunn
Differential Sensitivity to Escherichia coli Infection in Mice Lacking Tumor Necrosis Factor p55 or Interleukin-1 p80 Receptors
Arch Surg,
November 1, 1996;
131(11):
1216 - 1221.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. A. Boermeester, P. A. M. van Leeuwen, S. M. Coyle, G. J. Wolbink, C. E. Hack, and S. F. Lowry
Interleukin-1 Blockade Attenuates Mediator Release and Dysregulation of the Hemostatic Mechanism During Human Sepsis
Arch Surg,
July 1, 1995;
130(7):
739 - 748.
[Abstract]
[PDF]
|
|
|
|
|
