Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients*

Lowe, Peter N.; Galley, Helen F.; Abdel-Fattah, Abdel-Rahman; Webster, Nigel R.

doi:10.1097/00003246-200301000-00005

Cited by 143 publications

(103 citation statements)

References 31 publications

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“…The importance of IL-10 is also illustrated by its prognostic value in the critically ill. IL-10 administration reduces proinflammatory cytokine levels (81) and blocks monocyte activation (82), whereas endogenous plasma IL-10 relates to outcome in septic patients. Promoter polymorphisms for low IL-10 production predict higher death rates in severe sepsis (83), whereas HIV patients with polymorphisms for high IL-10 more often progress to AIDS (84). Chronic liver failure patients also show persistently high plasma IL-10 levels and often have prolonged sepsis (7).…”

Section: Was Detected (Panels A-c) Dcm/co (1-h Exposure) Caused Robumentioning

confidence: 99%

Heme Oxygenase-1 Couples Activation of Mitochondrial Biogenesis to Anti-inflammatory Cytokine Expression

Piantadosi

Withers

Bartz

et al. 2011

Journal of Biological Chemistry

231

184

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The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-inflammatory cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after LPS stimulated anti-inflammatory IL-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-␣ expression. This was accompanied by nuclear Nfe2l2 accumulation and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-inflammatory genes regulated by NF-〉. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (Gabpa), and MEF2, and for IL1Ra, included NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2 ؊/؊ mice. Nfe2l2 ؊/؊ mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2 ؊/؊ mice in sepsis also generated higher hepatic TNF-␣ mRNA levels, lower NRF-1 and PGC-1␣ mRNA levels, and no enhancement of anti-inflammatory Il10, Socs3, or bcl-x L gene expression. These findings disclose a highly structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis.Early survivors of severe sepsis often develop immune suppression (1, 2) and may later die with the multiple organ dysfunction syndrome (3). A key effector of multiple organ dysfunction syndrome is the liver, which is integral to the host response, especially in infections that activate Toll-like receptor 4 and NF-〉-dependent cytokine synthesis (4). The persistence of inflammatory cytokines such as TNF-␣ and IL-1␤ perpetuates immune activation, causing tissue damage and remodeling (5) and leads to sustained production of anti-inflammatory modulators and suppressors of adaptive immunity (6, 7).These anti-inflammatory modulators include the type II cytokine IL-10, the soluble IL-1 receptor antagonist (sIL-1Ra) 2 (5), and SOCS (suppressor of cytokine signaling) proteins (8). IL-10 is widely expressed in the liver (9, 10) by Kupffer cells (11), stellate cells (12), and hepatocytes (13), where it contributes to LPS tolerance (14). The IL-10 receptor activates JAK/STAT (Janus kinase/signal transducer and activator of transcription) to block the production of TNF-␣ and other NF-〉-dependent mediators (15), the basis for its anti-inflammatory effects (16). IL-10 also suppresses mononuclear cell function (17), and IL-10 secretion by macrophages and neutrophils negatively regulates the respon...

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Section: Was Detected (Panels A-c) Dcm/co (1-h Exposure) Caused Robumentioning

confidence: 99%

Heme Oxygenase-1 Couples Activation of Mitochondrial Biogenesis to Anti-inflammatory Cytokine Expression

Piantadosi

Withers

Bartz

et al. 2011

Journal of Biological Chemistry

231

184

View full text Add to dashboard Cite

show abstract

“…Furthermore, IL-10 plays a role in inhibition of cell adhesion molecules, monocyte chemotactic protein-1, tissue factor, fibrinogen, matrix metalloproteinase-9, T-lymphocyte granulocyte-macrophage colony-stimulation factor, inducible nitric oxide synthase and smooth muscle cell proliferation. [8][9][10] Several of these factors have been demonstrated to be involved in the restenotic process. 5,11 The interindividual difference among individuals in their ability to produce IL-10 appears to have a genetic origin.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention

et al. 2006

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“…[12][13][14][15] A number of studies have been presented providing evidence for associations between these IL-10 promoter variants and infectious or autoimmune diseases, including meningococcal infection, fatal septicemia, systemic lupus erythematodes, reactive arthritis, psoriasis, Sjogreń s syndrome, and multiple sclerosis. 10,12,[16][17][18][19][20] So far, it has not been studied, however, whether IL-10 promoter variants influence lymphocyte proliferation upon antigen stimulation, a major regulatory function attributed to IL-10.…”

Section: Introductionmentioning

confidence: 99%

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

et al. 2004

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Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.

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Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients*

Cited by 143 publications

References 31 publications

Heme Oxygenase-1 Couples Activation of Mitochondrial Biogenesis to Anti-inflammatory Cytokine Expression

Heme Oxygenase-1 Couples Activation of Mitochondrial Biogenesis to Anti-inflammatory Cytokine Expression

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention

Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen

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