Interleukin-10 Reduces Morbidity and Mortality in Murine Multiple Organ Dysfunction Syndrome (MODS)

Ferrer, Thomas J.; Webb, John W.; Wallace, Bonny H.; Bridges, C.D.B.; Palmer, Hal E.; Robertson, Ronald D.; Cone, John B.

doi:10.1006/jsre.1998.5372

Cited by 43 publications

(23 citation statements)

References 32 publications

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“…These findings are consistent with the observations of Jansen et al (11), who also found that although systemic pretreatment with rIL-10 was effective in improving outcome, posttreatment was not. However, other investigators have demonstrated a survival benefit when rIL-10 therapy was delivered to the mice when they developed symptoms of MSOF in the third phase of the zymosan-induced illness (30). The lack of an improvement in outcome with a posttreatment approach in the present studies as compared with the studies of Ferrer and his colleagues (30) is likely secondary to differing routes of administration, intratracheal vs systemic.…”

Section: Discussioncontrasting

confidence: 55%

Adenoviral Delivery of Human and Viral IL-10 in Murine Sepsis

Minter

Ferry

Murday

et al. 2001

The Journal of Immunology

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Adenovirus (Ad) gene therapy has been proposed as a drug-delivery system for the targeted administration of protein-based therapies, including growth factors and biological response modifiers. However, inflammation associated with Ad transduction has raised concern about its safety and efficacy in acute inflammatory diseases. In the present report, intratracheal and i.v. administration of a first-generation adenoviral recombinant (E1,E3 deleted) either containing an empty cassette or expressing the anti-inflammatory cytokines viral or human IL-10 (IL-10) was administered to mice subjected to zymosan-induced multisystem organ failure or to acute necrotizing pancreatitis. Pretreatment of mice with the intratracheal instillation of Ad expressing human IL-10 or viral IL-10 reduced weight loss, attenuated the proinflammatory cytokine response, and reduced mortality in the zymosan-induced model, whereas pretreatment with a control adenoviral recombinant did not significantly exacerbate the response. Pretreatment of mice with pancreatitis using adenoviral vectors expressing IL-10 significantly reduced the degree of pancreatic and liver injury and liver inflammation when administered systemically, but not intratracheally. We conclude that adenoviral vectors can be administered prophylactically in acute inflammatory syndromes, and expression of the anti-inflammatory protein IL-10 can be used to suppress the underlying inflammatory process.

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Section: Discussioncontrasting

confidence: 55%

Adenoviral Delivery of Human and Viral IL-10 in Murine Sepsis

Minter

Ferry

Murday

et al. 2001

The Journal of Immunology

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“…Specifically, in the patients treated with recombinant activated protein C, IL-10 levels were found to progressively increase until day 7, but, beyond that, plasma IL-10 levels declined back to baseline levels. Studies have demonstrated that elevated levels of IL-10 early postinsult confer protection following trauma, endotoxemia, and sepsis (23,24). In accordance with these findings, studies have also shown that reducing IL-10 at a later time point following the diagnosis of sepsis exerts beneficial effects (55).…”

Section: Figurementioning

confidence: 71%

“…In murine sepsis models, increases in IL-10 confer protection and are associated with survival (22,23). In humans, elevated levels of IL-10 early post-insult are protective (24) and may be beneficial to counter-regulate the early inflammatory response (25).…”

mentioning

confidence: 99%

Activated Protein C Up-Regulates IL-10 and Inhibits Tissue Factor in Blood Monocytes

Toltl¹,

Beaudin

Liaw

2008

The Journal of Immunology

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The protective effect of recombinant activated protein C therapy in patients with severe sepsis likely reflects the ability of recombinant activated protein C to modulate multiple pathways implicated in sepsis pathophysiology. In this study, we examined the effects of recombinant activated protein C on the anti-inflammatory cytokine IL-10 and on the procoagulant molecule tissue factor (TF) in LPS-challenged blood monocytes. Treatment of LPS-stimulated monocytes with recombinant activated protein C resulted in an up-regulation of IL-10 protein production and mRNA synthesis. The up-regulation of IL-10 required the serine protease activity of recombinant activated protein C and was dependent on protease-activated receptor-1, but was independent of the endothelial protein C receptor. At the intracellular level, p38 MAPK activation was required for recombinant activated protein C-mediated up-regulation of IL-10. We further observed that incubation of LPS-stimulated monocytes with recombinant activated protein C down-regulated TF Ag and activity levels. This anticoagulant effect of recombinant activated protein C was dependent on IL-10 since neutralization of endogenously produced IL-10 abrogated the effect. In patients with severe sepsis, plasma IL-10 levels were markedly higher in those treated with recombinant activated protein C than in those who did not receive recombinant activated protein C. This study reveals novel regulatory functions of recombinant activated protein C, specifically the up-regulation of IL-10 and the inhibition of TF activity in monocytes. Our data further suggest that these activities of recombinant activated protein C are directly linked: the recombinant activated protein C-mediated up-regulation of IL-10 reduces TF in circulating monocytes.

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“…Some studies suggest that increased IL-10 levels are an indicator of poor prognosis with higher risk for multiple organ failure, infection, and death (2)(3)(4)(5), whereas other studies indicate beneficial effects of early systemic IL-10 release following injury (6)(7)(8). In view of these diverse findings, we hypothesized that administration of IL-10 early in the course of hemorrhagic shock attenuates systemic and pulmonary inflammation.…”

Section: Introductionmentioning

confidence: 94%