Biology of interleukin-10 and its regulatory roles in sepsis syndromes

Scumpia, Philip O.; Moldawer, Lyle L.

doi:10.1097/01.ccm.0000186268.53799.67

Cited by 105 publications

(71 citation statements)

References 38 publications

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“…Administration of recombinant IL-10 inhibits LPS toxicity in mice (Howard et al 1993). Therefore, augmentation of IL-10 levels can be an effective way of treatment or prevention of sepsis (Scumpia and Moldawer, 2005). In the present study, decursinol was found to markedly augment LPS/GalN-induced plasma IL-10 levels.…”

Section: Discussionsupporting

confidence: 48%

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

Jung

Yan

Song

2008

Korean J Physiol Pharmacol

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The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol (1∼ 100 mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN-induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-α , IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

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Section: Discussionsupporting

confidence: 48%

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

Jung

Yan

Song

2008

Korean J Physiol Pharmacol

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“…Systemic injection of IL-10 has been reported to promote inflammation in humans (reviewed in Scumpia and Moldawer, 2005) and i.p. injection of IL-10 exacerbates clinical symptoms of experimental autoimmune encephalomyelitis in mice (Cannella et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking interleukin-10

Huey

McCusker

Kelley

2008

Journal of Neuroimmunology

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IL-10 reduces cytokine expression in non-muscle tissues, but its effect on skeletal muscle remains undefined. Therefore, we tested the hypothesis that endogenous IL-10 acts to reduce cytokines in the gastrocnemius muscle by comparing IL-6 and TNFα expression in wild-type (IL-10 +/+ ) and IL-10 deficient (IL-10 −/− ) mice following an inflammatory insult induced by peripheral LPS. IL-6 mRNA expression increased following LPS for both IL-10 +/+ and IL-10 −/− mice; the response was greater and prolonged in IL-10 −/− mice. Muscle TNFα mRNA also increased, but without differences between genotypes. IL-6 protein concentrations were elevated by LPS with a greater and prolonged response for IL-10 −/− mice, but TNFα did not change. These results provide the first in vivo evidence that endogenous IL-10 attenuates IL-6 expression by skeletal muscle in response to LPS.

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“…IL-10 is produced by monocytes/macrophages, dendritic cells, mast cells, NK cells, eosinophils, and neutrophils (4) and to a lesser extent by T and B cells (1) and regulates the synthesis of proinflammatory cytokines such as TNF-a (1,(4)(5)(6)(7). The role of IL-10, as a key antiinflammatory cytokine, is supported by amplified inflammatory responses in IL-10 knockout mice, mimicking inflammatory bowel disease (5,8). TNF-a is also secreted by monocytes/ macrophages in response to mitogens such as LPS (9), and dysregulated TNF-a production results in chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis (2).…”

mentioning

confidence: 99%

SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages

Okenwa

Kumar

Rego

et al. 2013

The Journal of Immunology

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The role of tyrosine phosphatase Src homology region 2 domain-containing phosphatase (SHP)-1 in LPS-activated cytokine production and inflammation was investigated by determining TNF-α and IL-10 production in splenic macrophages employing SHP-1–null (me/me) mouse model. LPS-stimulated me/me splenic macrophages secreted significantly less IL-10 with concomitantly elevated levels of TNF-α compared with wild-type (WT) macrophages irrespective of LPS dose and duration of stimulation. IL-10 significantly inhibited LPS-induced TNF-α production in both me/me and WT macrophages. The critical requirement for SHP-1 in regulating LPS-induced IL-10 and TNF-α production was confirmed by interfering with SHP-1 expression in WT macrophages and by reconstituting me/me macrophages with the SHP-1 gene. To delineate the role of SHP-1 in positive regulation of LPS-induced IL-10 production, signaling proteins representing SHP-1 targets were examined. The results reveal that tyrosine kinases Src and proline-rich tyrosine kinase 2 (Pyk2) regulate SHP-1–dependent LPS-induced IL-10 production and infer that optimal LPS-induced IL-10 production requires an assembly of a protein complex consisting of SHP-1–Pyk2–Src proteins. Moreover, LPS-induced IL-10 production also requires activation of the p38 MAPK independent of SHP-1 function. Overall, to our knowledge our results show for the first time that SHP-1 acts as a positive regulator of LPS-induced IL-10 production in splenic macrophages through two distinct and independent SHP-1–Pyk2–Src and p38 MAPK pathways.

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Biology of interleukin-10 and its regulatory roles in sepsis syndromes

Cited by 105 publications

References 38 publications

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

Exaggerated expression of skeletal muscle-derived interleukin-6, but not TNFα, in mice lacking interleukin-10

SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages

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