Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha. 1995

J Barsig, and S Küsters, and K Vogt, and H D Volk, and G Tiegs, and A Wendel
Biochemical Pharmacology, Faculty of Biology, University of Konstanz, Germany.

Interleukin (IL)-10 is known to protect mice against the lethal effects of lipopolysaccharides (LPS) and is considered to be an anti-inflammatory cytokine which suppresses the production of pro-inflammatory cytokines. We have examined the interactions of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) with IL-10. Neutralization of TNF-alpha in murine bone marrow-derived macrophages resulted in a significant reduction of LPS-inducible IL-10 production. In mice, injection of 5 mg/kg LPS induced circulating IL-10 with a biphasic time course exhibiting an early peak 1.5 h after challenge (synchronous with TNF-alpha) and, after a nadir at 6 h, a second increase between 8 and 12 h. Treatment of mice with neutralizing anti-mouse TNF-alpha antiserum significantly increased LPS-induced IL-10 plasma levels between 1.5 and 6 h but diminished those at 12 h, while circulating IL-6, interferon-gamma (IFN-gamma) and granulocyte colony-stimulating factor (G-CSF) concentrations were attenuated overall, without a biphasic response. Analysis of LPS-induced IL-10 mRNA expression in different tissues 1 h and 8 h after LPS or LPS plus anti-TNF-alpha revealed that the amount of transcripts in the liver correlated with circulating early and late IL-10 levels. Our findings suggest that endogenous TNF-alpha down-regulates the early and up-regulates the late LPS-induced IL-10 synthesis in vivo and that the liver is the major source of circulating IL-10 after stimulation with LPS.

UI MeSH Term Description Entries
D007153 Immunologic Deficiency Syndromes Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral. Antibody Deficiency Syndrome,Deficiency Syndrome, Immunologic,Deficiency Syndromes, Antibody,Deficiency Syndromes, Immunologic,Immunologic Deficiency Syndrome,Immunological Deficiency Syndromes,Antibody Deficiency Syndromes,Deficiency Syndrome, Antibody,Deficiency Syndrome, Immunological,Deficiency Syndromes, Immunological,Immunological Deficiency Syndrome,Syndrome, Antibody Deficiency,Syndrome, Immunologic Deficiency,Syndrome, Immunological Deficiency,Syndromes, Antibody Deficiency,Syndromes, Immunologic Deficiency,Syndromes, Immunological Deficiency
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin

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