Increased Soluble Tumor Necrosis Factor Receptor Levels in the Serum of Elderly People

Background: Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. Objective:...

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Published inGerontology (Basel) Vol. 46; no. 4; pp. 185 - 188
Main Authors Hasegawa, Yoshiya, Sawada, Makoto, Ozaki, Norio, Inagaki, Toshiaki, Suzumura, Akio
Format Journal Article
LanguageEnglish
Published Basel, Switzerland Karger 01.07.2000
S. Karger AG
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Abstract Background: Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. Objective: To discuss possible causes of increased risks for infectious disease and cancer seen in the elderly. Methods: The participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1α, IL-1β, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-α were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R. Results: IL-1α, IL-1β, IL-6, and TNF-α were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations. Conclusions: Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
AbstractList Background: Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. Objective: To discuss possible causes of increased risks for infectious disease and cancer seen in the elderly. Methods: The participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1α, IL-1β, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-α were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R. Results: IL-1α, IL-1β, IL-6, and TNF-α were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations. Conclusions: Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. To discuss possible causes of increased risks for infectious disease and cancer seen in the elderly. The participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1alpha, IL-1beta, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-alpha were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R. IL-1alpha, IL-1beta, IL-6, and TNF-alpha were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations. Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase. To discuss possible causes of increased risks for infectious disease and cancer seen in the elderly. The participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1alpha, IL-1beta, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-alpha were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R. IL-1alpha, IL-1beta, IL-6, and TNF-alpha were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations. Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
BACKGROUNDSoluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding with receptors on target cells. In a variety of pathologic situations, the concentrations of sTNF receptors (R) increase.OBJECTIVETo discuss possible causes of increased risks for infectious disease and cancer seen in the elderly.METHODSThe participants were healthy subjects (n = 48) of three age groups (young, middle-aged, and elderly). Patients with senile dementia of Alzheimer type (n = 25) were also studied. For detection of cytokines, interleukin (IL) 1alpha, IL-1beta, IL-6, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor, and TNF-alpha were measured in serum by enzyme-linked immunosorbent assays, as were soluble (s) IL-1 receptor antagonist (IL-1ra), sIL-6R, p55sTNF-R, and p75sTNF-R.RESULTSIL-1alpha, IL-1beta, IL-6, and TNF-alpha were not detected, and sIL-6R and IL-1ra concentrations were not significantly different between the three age groups. However, sTNF-R and M-CSF were increased in sera from the elderly, both healthy and demented. A significant correlation was seen between sTNF-R and M-CSF concentrations.CONCLUSIONSIncreased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
Author Hasegawa, Yoshiya
Ozaki, Norio
Inagaki, Toshiaki
Sawada, Makoto
Suzumura, Akio
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  surname: Suzumura
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Cites_doi 10.1016/0014-5793(89)80449-1
10.1084/jem.172.2.599
10.1016/S1359-6101(96)00026-3
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Issue 4
Keywords Soluble interleukin-6 receptor
Soluble tumor necrosis factor receptors
Proinflammatory cytokines
Soluble cytokine receptors
Elderly
Interleukin-1 receptor antagonist
Human
Nervous system diseases
Senescence
Pathophysiology
Alzheimer disease
Cytokine
Malignant tumor
Cerebral disorder
Infection
Granulocyte colony stimulating factor
Tumor necrosis factor
Central nervous system disease
Interleukin 1
Degenerative disease
Macrophage colony stimulating factor
Biological receptor
Language English
License Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
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PublicationTitle Gerontology (Basel)
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Heller RA, Song K, Onasch MA, Fisher WH, Chang D, Ringold GM: Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. Proc Natl Acad Sci USA 1990;87:6151-6158.2166946
Grosen E, Yamamoto RS, Ioli G: Primary tumor cultures from patients with gynecologic malignancies release TNF/LT blocking factors in vitro (abstract). Third Int Workshop on Cytokines, Amsterdam 1991, pp 501-509.
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Lehtonen L, Eskola J, Vainio O, Lehtonen A: Changes in lymphocyte subsets and immune competence in very advanced age. J Gerontol 1990;45:M108-M116.2335720
Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R: Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 1993;23:2375-2381.8370415
Aderka D: The potential biological and clinical significance of the soluble tumor necrosis factor receptors. Cytokine Growth Factor Rev 1996;7:231-241.897147810.1016/S1359-6101(96)00026-3
Nagelkerken L, Hertogh-Huijbregts A, Dobber R, Drager A: Age-related changes in lymphokine production related to a decreased number of CD45RBhi CD4+ T cells. Eur J Immunol 1991;21:273-280.1671835
Tartaglia LA, Goeddel DV: Two TNF receptors. Immunol Today 1992;13:151-153.1322675
Loetscher H, Steinmetz M, Lesslauer W: Tumor necrosis factor: Receptors and inhibitors. Cancer Cells 1991;3:221-226.1654969
Cossarizza A, Monti D, Cantini M, Paganelli R, Montagnani G, Cadossi R, Bersani F, Franceschi C: Extremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen-stimulated human lymphocytes from old subjects. FEBS Lett 1989;248:141-152.278593310.1016/0014-5793(89)80449-1
Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF: TNF-soluble receptors circulate during experimental and clinical inflammation and can protect against excessive TNFα in vitro and in vivo. Proc Natl Acad Sci USA 1992;89:4845-4852.1317575
Porteu F, Nathan C: Shedding of tumor necrosis factors by activated human neutrophils. J Exp Med 1990;172:599-608.216512810.1084/jem.172.2.599
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Snippet Background: Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF...
Soluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF binding...
BACKGROUNDSoluble (s) forms of tumor necrosis factor (TNF) receptors are the only natural molecules known to interfere with TNF activity by competing for TNF...
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SubjectTerms Adult
Aged
Aged, 80 and over
Aging - blood
Alzheimer Disease - blood
Antigens, CD - blood
Biological and medical sciences
Clinical Section
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Female
Humans
Macrophage Colony-Stimulating Factor - blood
Male
Medical sciences
Middle Aged
Neurology
Receptors, Tumor Necrosis Factor - blood
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Reference Values
Solubility
Title Increased Soluble Tumor Necrosis Factor Receptor Levels in the Serum of Elderly People
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Volume 46
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