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Interleukin-1 and interleukin-1 antagonism
CA Dinarello
Department of Medicine, Tufts University School of Medicine, Boston, MA.
The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue
and organ system. IL-1 is the prototype of the pro-inflammatory cytokines
in that it induces the expression of a variety of genes and the synthesis
of several proteins that, in turn, induce acute and chronic inflammatory
changes. IL-1 is also the prototypic "alarm" cytokine in that it brings
about increases in a variety of defense mechanisms, particularly
immunologic and hematologic responses. Most studies on the biology of IL-1
have been performed in animals, but human subjects have recently been
injected with recombinant IL-1 and the results confirm the two fundamental
properties of IL-1 as being both a mediator of disease as well as of host
defense. However, in either situation, over or continued production of IL-1
leads to debilitation of normal host functions; therefore, reduction of
IL-1 synthesis or its effects becomes a target of therapy in many diseases.
In this review, the structure, gene expression, synthesis, and secretion of
IL-1 are described. In addition, the two IL-1 surface receptors, possible
signal transduction mechanisms, various biologic activities, and production
of IL-1 during disease states are discussed. Similarities and differences
between IL-1, tumor necrosis factor, and IL-6 are presented. Although
various agents for reducing the synthesis and/or for antagonizing the
effects of IL-1 have been proposed, the recent cloning of a naturally
occurring IL-1 receptor antagonist (IL- 1ra) has opened new experimental
and clinical approaches. The ability of this IL-1ra to block the triggering
of IL-1 receptors in animals without agonist effects has reduced the
severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory
bowel disease, experimental arthritis, and the spontaneous proliferation of
human leukemic cells.
Volume 77,
Issue 8,
pp. 1627-1652,
04/15/1991
Copyright © 1991 by The American Society of Hematology

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S. Nakae, C. Naruse-Nakajima1, K. Sudo, R. Horai, M. Asano, and Y. Iwakura
IL-1{alpha}, but not IL-1{beta}, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity
Int. Immunol.,
December 1, 2001;
13(12):
1471 - 1478.
[Abstract]
[Full Text]
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G.-M. Deng, Z.-Q. Liu, and A. Tarkowski
Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis
J. Immunol.,
October 15, 2001;
167(8):
4616 - 4626.
[Abstract]
[Full Text]
[PDF]
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S. P. Matzer, T. Baumann, N. W. Lukacs, M. Rollinghoff, and H. U. Beuscher
Constitutive Expression of Macrophage-Inflammatory Protein 2 (MIP-2) mRNA in Bone Marrow Gives Rise to Peripheral Neutrophils with Preformed MIP-2 Protein
J. Immunol.,
October 15, 2001;
167(8):
4635 - 4643.
[Abstract]
[Full Text]
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S E Francis, N J Camp, A J Burton, R M Dewberry, J Gunn, A Stephens-Lloyd, D C Cumberland, A Gershlick, and D C Crossman
Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty
Heart,
September 1, 2001;
86(3):
336 - 340.
[Abstract]
[Full Text]
[PDF]
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S. S. Witkin, I. M. Linhares, S. Gerber, M. E. Caetano, and A. C. Segurado
Interleukin-1 Receptor Antagonist Gene Polymorphism and Circulating Levels of Human Immunodeficiency Virus Type 1 RNA in Brazilian Women
J. Virol.,
July 1, 2001;
75(13):
6242 - 6244.
[Abstract]
[Full Text]
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S. Nakae, M. Asano, R. Horai, N. Sakaguchi, and Y. Iwakura
IL-1 Enhances T Cell-Dependent Antibody Production Through Induction of CD40 Ligand and OX40 on T Cells
J. Immunol.,
July 1, 2001;
167(1):
90 - 97.
[Abstract]
[Full Text]
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M Takashima, T Furuta, H Hanai, H Sugimura, and E Kaneko
Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils
Gut,
June 1, 2001;
48(6):
765 - 773.
[Abstract]
[Full Text]
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E. La and S. M. Fischer
Transcriptional Regulation of Intracellular IL-1 Receptor Antagonist Gene by IL-1{{alpha}} in Primary Mouse Keratinocytes
J. Immunol.,
May 15, 2001;
166(10):
6149 - 6155.
[Abstract]
[Full Text]
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T. G. Moreels, J. G. De Man, J. J. Bogers, B. Y. De Winter, G. Vrolix, A. G. Herman, E. A. Van Marck, and P. A. Pelckmans
Effect of Schistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility
Am J Physiol Gastrointest Liver Physiol,
May 1, 2001;
280(5):
G1030 - G1042.
[Abstract]
[Full Text]
[PDF]
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P. Cooper, S. Potter, B. Mueck, S. Yousefi, and G. Jarai
Identification of genes induced by inflammatory cytokines in airway epithelium
Am J Physiol Lung Cell Mol Physiol,
May 1, 2001;
280(5):
L841 - L852.
[Abstract]
[Full Text]
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V N Foltyn and T D Golan
In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from premorbid SLE mice
Lupus,
April 1, 2001;
10(4):
272 - 283.
[Abstract]
[PDF]
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C. L. Cubitt, R. N. Lausch, and J. E. Oakes
Synthesis of Type II Interleukin-1 Receptors by Human Corneal Epithelial Cells but not by Keratocytes
Invest. Ophthalmol. Vis. Sci.,
March 1, 2001;
42(3):
701 - 704.
[Abstract]
[Full Text]
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K. Shirakawa, H. Tsuda, Y. Heike, K. Kato, R. Asada, M. Inomata, H. Sasaki, F. Kasumi, M. Yoshimoto, T. Iwanaga, et al.
Absence of Endothelial Cells, Central Necrosis, and Fibrosis Are Associated with Aggressive Inflammatory Breast Cancer
Cancer Res.,
January 1, 2001;
61(2):
445 - 451.
[Abstract]
[Full Text]
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H. Yamagishi, T. Yokoo, T. Imasawa, T. Mitarai, T. Kawamura, and Y. Utsunomiya
Genetically Modified Bone Marrow-Derived Vehicle Cells Site Specifically Deliver an Anti-Inflammatory Cytokine to Inflamed Interstitium of Obstructive Nephropathy
J. Immunol.,
January 1, 2001;
166(1):
609 - 616.
[Abstract]
[Full Text]
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E. Castigli, C. Arcuri, L. Giovagnoli, R. Luciani, L. Giovagnoli, T. Secca, G. L. Gianfranceschi, and V. Bocchini
Interleukin-1beta induces apoptosis in GL15 glioblastoma-derived human cell line
Am J Physiol Cell Physiol,
December 1, 2000;
279(6):
C2043 - C2049.
[Abstract]
[Full Text]
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R. Dewberry, H. Holden, D. Crossman, and S. Francis
Interleukin-1 Receptor Antagonist Expression in Human Endothelial Cells and Atherosclerosis
Arterioscler Thromb Vasc Biol,
November 1, 2000;
20(11):
2394 - 2400.
[Abstract]
[Full Text]
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F. Conti, S. Breton, F. Batteux, V. Furlan, D. Houssin, B. Weill, and Y. Calmus
Defective Interleukin-1 Receptor Antagonist Production Is Associated with Resistance of Acute Liver Graft Rejection to Steroid Therapy
Am. J. Pathol.,
November 1, 2000;
157(5):
1685 - 1692.
[Abstract]
[Full Text]
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M. H Schiff
Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis
Ann Rheum Dis,
November 1, 2000;
59(90001):
i103 - 108.
[Abstract]
[Full Text]
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H.-H. Chou, S. Takashiba, H. Maeda, K. Naruishi, F. Nishimura, H. Arai, H.-k. Lu, and Y. Murayama
Induction of Intracellular Interleukin-1 {beta} Signals via Type II Interleukin-1 Receptor in Human Gingival Fibroblasts
Journal of Dental Research,
September 1, 2000;
79(9):
1683 - 1688.
[Abstract]
[PDF]
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T. Hochepied, W. Van Molle, F. G. Berger, H. Baumann, and C. Libert
Involvement of the Acute Phase Protein alpha 1-Acid Glycoprotein in Nonspecific Resistance to a Lethal Gram-negative Infection
J. Biol. Chem.,
May 12, 2000;
275(20):
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[Abstract]
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J. M. Sanz and F. D. Virgilio
Kinetics and Mechanism of ATP-Dependent IL-1{beta} Release from Microglial Cells
J. Immunol.,
May 1, 2000;
164(9):
4893 - 4898.
[Abstract]
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J. M. Daun, R. W. Ball, and J. G. Cannon
Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender
Am J Physiol Regulatory Integrative Comp Physiol,
April 1, 2000;
278(4):
R855 - R862.
[Abstract]
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J. F. Frøen, H. Akre, B. Stray-Pedersen, and O. D. Saugstad
Adverse Effects of Nicotine and Interleukin-1beta on Autoresuscitation After Apnea in Piglets: Implications for Sudden Infant Death Syndrome
Pediatrics,
April 1, 2000;
105(4):
52e - 52.
[Abstract]
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R. Kekuda, F. H. Leibach, T. C. Furesz, C. H. Smith, and V. Ganapathy
Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta
J. Pharmacol. Exp. Ther.,
March 1, 2000;
292(3):
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T. Mühlberg, W. Joba, C. Spitzweg, H.-D. Schworm, H.-J. Heberling, and A. E. Heufelder
Interleukin-1 Receptor Antagonist Ribonucleic Acid and Protein Expression by Cultured Graves' and Normal Orbital Fibroblasts Is Differentially Modulated by Dexamethasone and Irradiation
J. Clin. Endocrinol. Metab.,
February 1, 2000;
85(2):
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P H McGuinness, D Painter, S Davies, and G W McCaughan
Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection
Gut,
February 1, 2000;
46(2):
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[Abstract]
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F. Galeazzi, E. M. Haapala, N. van Rooijen, B. A. Vallance, and S. M. Collins
Inflammation-induced impairment of enteric nerve function in nematode-infected mice is macrophage dependent
Am J Physiol Gastrointest Liver Physiol,
February 1, 2000;
278(2):
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Q. He and M. C. LaPointe
Interleukin-1{beta} Regulates the Human Brain Natriuretic Peptide Promoter via Ca2+-Dependent Protein Kinase Pathways
Hypertension,
January 1, 2000;
35(1):
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[Abstract]
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C. Metais, J. Li, J. Li, M. Simons, and F. W. Sellke
Serotonin-Induced Coronary Contraction Increases After Blood Cardioplegia-Reperfusion : Role of COX-2 Expression
Circulation,
November 9, 1999;
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[Abstract]
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M. H. A. M. Veltrop, H. Beekhuizen, and J. Thompson
Bacterial Species- and Strain-Dependent Induction of Tissue Factor in Human Vascular Endothelial Cells
Infect. Immun.,
November 1, 1999;
67(11):
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Z. Estrov, S. K. Manna, D. Harris, Q. Van, E. H. Estey, H. M. Kantarjian, M. Talpaz, and B. B. Aggarwal
Phenylarsine Oxide Blocks Interleukin-1beta -Induced Activation of the Nuclear Transcription Factor NF-kappa B, Inhibits Proliferation, and Induces Apoptosis of Acute Myelogenous Leukemia Cells
Blood,
October 15, 1999;
94(8):
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[Abstract]
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E. A. Hammond, D. Smart, S. Toulmond, N. Suman-Chauhan, J. Hughes, and M. D. Hall
The interleukin-1 type I receptor is expressed in human hypothalamus
Brain,
September 1, 1999;
122(9):
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[Abstract]
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I. Ikonomidis, F. Andreotti, E. Economou, C. Stefanadis, P. Toutouzas, and P. Nihoyannopoulos
Increased Proinflammatory Cytokines in Patients With Chronic Stable Angina and Their Reduction By Aspirin
Circulation,
August 24, 1999;
100(8):
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[Abstract]
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S. Lemay, T. V. Lebedeva, and A. K. Singh
Inhibition of Cytokine Gene Expression by Sodium Salicylate in a Macrophage Cell Line through an NF-kappa B-Independent Mechanism
Clin. Vaccine Immunol.,
July 1, 1999;
6(4):
567 - 572.
[Abstract]
[Full Text]
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R. M. Strieter, S. L. Kunkel, M. P. Keane, and T. J. Standiford
Chemokines in Lung Injury: Thomas A. Neff Lecture
Chest,
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[Full Text]
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J. M. Perlman
Maternal Fever and Neonatal Depression: Preliminary Observations
Clinical Pediatrics,
June 1, 1999;
38(5):
287 - 291.
[Abstract]
[PDF]
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W. P. Luk, Y. Zhang, T. D. White, F. A. Lue, C. Wu, C.-G. Jiang, L. Zhang, and H. Moldofsky
Adenosine: a Mediator of Interleukin-1beta -Induced Hippocampal Synaptic Inhibition
J. Neurosci.,
June 1, 1999;
19(11):
4238 - 4244.
[Abstract]
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C. A. Felix and B. J. Lange
Leukemia in Infants
Oncologist,
June 1, 1999;
4(3):
225 - 240.
[Abstract]
[Full Text]
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M. Watanabe, T. Tabata, J.-I. Huh, T. Inai, A. Tsuboi, K. Sasaki, and Y. Endo
Possible Involvement of Histamine in Muscular Fatigue in Temporomandibular Disorders: Animal and Human Studies
Journal of Dental Research,
March 1, 1999;
78(3):
769 - 775.
[Abstract]
[PDF]
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