Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha.
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Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha. / Barsig, J; Küsters, S; Vogt, K; Volk, H D; Tiegs, Gisa; Wendel, A.
In: EUR J IMMUNOL, Vol. 25, No. 10, 10, 1995, p. 2888-2893.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha.
AU - Barsig, J
AU - Küsters, S
AU - Vogt, K
AU - Volk, H D
AU - Tiegs, Gisa
AU - Wendel, A
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Animals
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred BALB C
KW - Organ Specificity
KW - RNA, Messenger/biosynthesis/genetics
KW - Mice, Nude
KW - Mice, SCID
KW - Interferon-gamma/biosynthesis
KW - Lipopolysaccharides/pharmacology
KW - Bacterial Toxins/pharmacology
KW - Bone Marrow Cells
KW - Endotoxins/pharmacology
KW - Gene Expression Regulation/drug effects
KW - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
KW - Immunologic Deficiency Syndromes/immunology/physiopathology
KW - Interleukin-10/biosynthesis/genetics
KW - Macrophages/drug effects/metabolism
KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors/physiology
KW - Animals
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred BALB C
KW - Organ Specificity
KW - RNA, Messenger/biosynthesis/genetics
KW - Mice, Nude
KW - Mice, SCID
KW - Interferon-gamma/biosynthesis
KW - Lipopolysaccharides/pharmacology
KW - Bacterial Toxins/pharmacology
KW - Bone Marrow Cells
KW - Endotoxins/pharmacology
KW - Gene Expression Regulation/drug effects
KW - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
KW - Immunologic Deficiency Syndromes/immunology/physiopathology
KW - Interleukin-10/biosynthesis/genetics
KW - Macrophages/drug effects/metabolism
KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors/physiology
M3 - SCORING: Journal article
VL - 25
SP - 2888
EP - 2893
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 10
M1 - 10
ER -
