Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.

Gérard, Catherine; Bruyns, Catherine; Marchant, Arnaud; Abramowicz, Daniel; Vandenabeele, Peter; Delvaux, Anne; Fiers, Walter; Goldman, Michel; Velu, Thierry

doi:10.1084/jem.177.2.547

Cited by 760 publications

(376 citation statements)

References 24 publications

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“…Murine IL-10 was cloned and expressed as previously described (32). The biological activity of IL-10 was verified in an LPS-mediated lethal-shock model (27).…”

Section: Methodsmentioning

confidence: 99%

“…Endotoxic shock and cutaneous inflammatory responses were enhanced in IL-10 knockouts (53,54). Likewise, blocking of endogenous IL-10 with neutralizing antibodies enhanced endotoxic shock, IgG immune complex-induced lung injury, and the severity of CIA (27,28,30). The latter study by Kunkel's group showed an increase in IL-10 at the mRNA and protein levels in joint tissues from the onset of arthritis, and accelerated expression of CIA was noted when anti-IL-10 treatment was started on day 24.…”

Section: Days After Immunizationmentioning

confidence: 96%

“…This may provide a reason for uncontrolled cytokine production in RA, and may also offer a therapeutic approach. Efficacy of the in vivo administration of IL-4 or IL-10 has already been shown in TNF/IL-l-dependent animal models, such as endotoxin-induced lethality and IgG immune complexinduced lung injury (27,28), but data in experimental arthritis are scant. Allen et a1 (29) showed that sustained treatment with IL-4 suppressed the chronic, but not the acute, phase of streptococcal cell wall (SCW)-induced arthritis in rats and demonstrated up-regulated IL-1Ra mRNA levels in the monocytes of these animals.…”

mentioning

confidence: 99%

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Role of interleukin‐4 and interleukin‐10 in murine collagen‐induced arthritis. Protective effect of interleukin‐4 and interleukin‐10 treatment on cartilage destruction

Joosten

Lubberts

Durez

et al. 1997

Arthritis & Rheumatism

374

246

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Objective. To examine the role of endogenous interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10) and the therapeutic effect of the addition of IL‐4 and IL‐10 in early and established murine collagen‐induced arthritis (CIA). Methods. Murine recombinant IL‐4, IL‐10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7–10 days of CIA in DBA/1 mice. Anti‐IL‐4, anti–IL‐10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription‐polymerase chain reaction (RT‐PCR) analyses were performed at the end of the treatment period. Results. IL‐4 alone did not provoke any effect, IL‐10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL‐4/IL‐10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor α (TNFα) and IL‐1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL‐1 receptor antagonist (IL‐1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNFα and IL‐1, with concomitant up‐regulation of the IL‐1Ra/IL‐1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti–IL‐10 antibodies. This expression could be further optimized with a combination of anti–IL‐4 and anti–IL‐10 antibodies, although anti–IL‐4 alone was without effect. Conclusion. Our data are consistent with a dominant role of IL‐10 in the natural suppression of arthritis expression, whereas combined treatment with IL‐4 and IL‐10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.

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“…Murine IL-10 was cloned and expressed as previously described (32). The biological activity of IL-10 was verified in an LPS-mediated lethal-shock model (27).…”

Section: Methodsmentioning

confidence: 99%

Section: Days After Immunizationmentioning

confidence: 96%

mentioning

confidence: 99%

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Role of interleukin‐4 and interleukin‐10 in murine collagen‐induced arthritis. Protective effect of interleukin‐4 and interleukin‐10 treatment on cartilage destruction

Joosten

Lubberts

Durez

et al. 1997

Arthritis & Rheumatism

374

246

View full text Add to dashboard Cite

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“…particularly due to inhibition of TNF- § production [10,11]. This demonstrates that the main in vivo function of IL-10 is to modulate the antimicrobial response which, when uncontrolled, can harm not only pathogens but as well the host itself.…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

et al. 2004

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Interleukin‐10 (IL‐10), originally identified as an inhibitor of pro‐inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL‐10 functions. We aimed at identifying possiblemediators of in vitro IL‐10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with 12,000 genes. To prove relevance of the identified genes for the clinicalsituation we compared these in vitro results with genes being regulated by IL‐10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL‐10 therapy. A high proportion of the 1,600 genes up‐regulated and 1,300 genes down‐regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL‐10, can be assigned to known IL‐10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL‐10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up‐regulation of heme oxygenase‐1 (HO‐1). However, we demonstrate that the anti‐inflammatory mechanisms of IL‐10 remain functional even when HO‐1 is irreversibly inhibited.

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“…ICAM-1 initiates adhesion and transendothelial migration of circulating leukocytes [42] . Evidence has also suggested that IL-10 may have a therapeutic potential in acute and chronic inflammatory disease [44] . Exogenous administration of recombinant IL-10 protects mice from lethal endotoxemia by reducing TNF-α release [44] .…”

Section: Discussionmentioning

confidence: 99%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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IntroductionHeatstroke is defined as a form of excessive hyperthermia (>40 °C) associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system (CNS) disorders such as delusion, convulsion and coma predominate [1] . Our recent results have demonstrated that heatstroke rodents display hypotension, systemic inflammatory responses, hypothalamic ischemia and neuronal damage, and multi-organ dysfunction [2][3][4] .Kynurenic acid (KYNA) or its metabolic precursor L-kynurenine may be of therapeutic value in neurodegenerative diseased models [5,6] . For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning. Accordingly, the temporal profiles of the apoptotic cell numbers of spleen, kidney, liver, lung, and hypothalamus, Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke Aim: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. Methods: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 ºC for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 ºC) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. Results: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tunor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 lev...

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Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.

Cited by 760 publications

References 24 publications

Role of interleukin‐4 and interleukin‐10 in murine collagen‐induced arthritis. Protective effect of interleukin‐4 and interleukin‐10 treatment on cartilage destruction

Role of interleukin‐4 and interleukin‐10 in murine collagen‐induced arthritis. Protective effect of interleukin‐4 and interleukin‐10 treatment on cartilage destruction

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

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