Cited by 1,768Cytokine Signaling Pathways and InteractionsImmune Response and InflammationT-cell and B-cell Immunology

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Impaired immune and acute-phase responses in interleukin-6-deficient mice

Kopf, Manfred, Baumann, Heinz, Freer, Giulia, Freudenberg, Marina, Lamers, Marinus, Kishimoto, Tadamitsu, Zinkernagel, Rolf, Bluethmann, Horst, Köhler, Georges·1994·Nature

DOI 10.1038/368339a0

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Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.

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Background
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Background
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Background
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Result
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BackgroundMethod
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BackgroundMethod
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“LLO was shown to be capable of inducing the expression of various cytokine genes, including IL-1 , IL-6, IL-10, IL-12 p35, IL-12 p40, and TNF- genes, by CD11b cells.”
Influential
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“body responses against vesicular stomatitis virus [8, 9], and”
Background
The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14-independent.
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Self-citation
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TRAIL/Apo-2 Ligand Induces Primary Plasma Cell Apoptosis
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“IgA responses are defective in the absence of IL-6 (20, 21).”
Background
Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor.
Mitnick, M., Grey, A., Masiukiewicz, U., Bartkiewicz, M., Rios-Velez, L., Friedman, S., Xu, L.-M., Horowitz, M., & Insogna, K. (2001) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.3.e405 · Cited by 80
“IL-6 knockout mice exhibit impaired synthesis of acute-phase proteins (25), whereas hepatic overexpression of IL-6 in mice leads to exaggerated production of acute-phase proteins, an effect that is augmented by coexpression of the IL-6sR (35).”
Background
Shared Cytokine Signaling Receptors: Structural Insights from the Gp130 System
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Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development
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Interleukin 6, but Not T Helper 2 Cytokines, Promotes Lung Carcinogenesis
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Background
Acute Phase Proteins and Transformed Cells
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Immunological Studies of Chronic Ocular Toxoplasmosis: Up-Regulation of Major Histocompatibility Complex Class I and Transforming Growth Factor β and a Protective Role for Interleukin-6
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“Female mice of the 129/SVJ strain (WT) and IL-6 mice of the same genetic background, as previously described (17), were”
BackgroundResultInfluential
Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long‐Term Clinical Trial Safety Data in Rheumatoid Arthritis
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Background
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Masiá, M., Fernández‐González, M., Padilla, S., Ortega, P., García, J. A., Agulló, V., García‐Abellán, J., Telenti, G., Guillén, L., & Gutiérrez, F. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102999 · Cited by 74
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Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation
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“The pro-inflammatory effects include the essential role of IL-6 in IgA production (17), turpentine-induced tissue inflammation (18), Lyme arthritis (19), tumor infiltration (20), Ag-induced arthritis (21), carrageenan-induced pleural inflammation (11), and the control and/or irradication of infections caused byMycobac…”
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Leptin stimulates fetal and adult erythroid and myeloid development.
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GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium
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Background
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Self-citation
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“Although IL-6 normally plays a key role in maintaining immunity [25, 26], abnormally high levels of this cytokine in sera and tissues of burn patients correlate with the severity of injury and subsequent morbidity and mortality, even in the absence of sepsis [18, 21, 27–29].”
Background
The residual megakaryocyte and platelet production in c-mpl-deficient mice is not dependent on the actions of interleukin-6, interleukin-11, or leukemia inhibitory factor.
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Regulation of emergency granulopoiesis during infection
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Background
A model for cancer-suppressive inflammation
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Microarray‐based understanding of normal and malignant plasma cells
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“Mice lacking this gene are impaired in T-cell-dependent antibody response (30), and conversely, transgenic mice expressing IL6 under the control of the Em enhancer promoter trigger a fatal polyclonal plasmacytosis (31).”
Background
Lack of Interleukin-6 (IL-6) Enhances Susceptibility to Infection but Does Not Alter Latency or Reactivation of Herpes Simplex Virus Type 1 in IL-6 Knockout Mice
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BackgroundMethod
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“For example, mice deficient in IL-1b (18), IL-1 receptor type I (34), TNF (37), or IL-6 (19, 29) all demonstrate a relatively normal LPS response, providing evidence for significant redundancy of function in cytokine signaling.”
Background

Authors: Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G.
Affiliations: University of Zurich (CH)
Max Planck Society (DE)
The University of Osaka (JP)
F. Hoffmann-La Roche AG (CH)
Roswell Park Comprehensive Cancer Center (US)
ORCID: Freer, Giulia
Freudenberg, Marina
Kishimoto, Tadamitsu
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1994-03-24
Volume: 368
Issue: 6469
Pages: 339-342
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/368339a0
OpenAlex: W2067761476
Cited by: 1,768
References: 0
Citations by year: 2026: 20 · 2025: 33 · 2024: 23 · 2023: 36 · 2022: 44 · 2021: 58 · 2020: 43 · 2019: 52 · 2018: 46 · 2017: 60 · 2016: 57 · 2015: 44 · 2014: 48 · 2013: 56 · 2012: 64
FWCI: 28.71
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: interleukin-6, IL-6-deficient mice, gene disruption, acute phase response, immune response, vaccinia virus infection, Listeria monocytogenes, T cell-dependent antibody response, vesicular stomatitis virus, lipopolysaccharide, gp130, cytokine redundancy, inflammation, macrophages, liver
MeSH terms: Acute-Phase Reaction, Animals, B-Lymphocytes, Immunity, Listeriosis, Lymphoid Tissue, Mice, Inbred C57BL, RNA, Messenger, T-Lymphocytes, Vesicular stomatitis Indiana virus, Interleukin-6, Rhabdoviridae Infections, Mice

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Impaired immune and acute-phase responses in interleukin-6-deficient mice

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