Interleukin-10 is upregulated in LPS tolerance.
Lipopolysaccharide (LPS) stimulation of the human monocytic cell line Mono Mac 6 leads to rapid expression of both the pro-inflammatory cytokine tumor necrosis factor (TNF) and the anti-inflammatory cytokine interleukin-10 (IL-10). Preculture of these cells with a low dose of LPS for 2 days rendered the cells tolerant to subsequent stimulation, in that TNF gene expression is only minimal, both at the mRNA and at the protein level. IL-10 shows a reciprocal pattern, however, as expression of this gene is upregulated in precultured cells, and it will further increase upon subsequent stimulation. Although TNF has been shown to induce IL-10, and IL-10 was found to downregulate TNF, this reciprocal regulation does not explain the pattern observed in LPS tolerance in Mono Mac 6, since neutralizing antibodies against TNF and IL-10 could not prevent upregulation of IL-10 and downregulation of TNF, respectively. Treatment of Mono Mac 6 cells during LPS preculture with interferon-gamma (IFN-gamma) could, however, reverse tolerance: LPS/IFN-gamma precultured cells produced high levels of TNF transcripts upon subsequent stimulation, while the response of the IL-10 gene was attenuated. The data show that LPS tolerance does not involve a passive downregulation of all types of monocyte functions, but it is an orchestrated response with downregulation of pro- and upregulation of anti-inflammatory cytokines.
Frankenberger
M
M
Institute for Immunology, University of Munich, Germany.
Pechumer
H
H
Ziegler-Heitbrock
H W
HW
D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D017931:DNA Primers; D004361:Drug Tolerance; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000906:Antibodies; D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10