Reversal of Immunoparalysis in Humans<i>In Vivo</i>

Leentjens, Jenneke; Kox, Matthijs; Koch, Rebecca M.; Preijers, Frank; Joosten, Leo A. B.; Hoeven, Johannes G. van der; Netea, Mihai G.; Pickkers, Peter

doi:10.1164/rccm.201204-0645oc

Cited by 203 publications

(107 citation statements)

References 52 publications

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“…It is normally not detectable in the plasma of healthy humans, but levels can be elevated in patients with sepsis [66]. Recent evidence suggests that IFN-γ may play an important role in the reversal of sepsis-induced immunoparalysis [67,68]. In contrast, expression of IL-10 is largely associated with anti-inflammatory functions, such as suppression of pro-inflammatory mediators (e.g.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

152

160

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Objectives To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design Randomized, placebo-controlled, trial. Setting Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients 30 adult ICU patients. Interventions Placebo (n=10) versus 200,000 IU cholecalciferol (n=10) versus 400,000 IU cholecalciferol (n=10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D (25OHD), as well as vitamin D binding protein and albumin to calculate bioavailable 25OHD. Plasma LL-37 and high sensitivity C-reactive protein (hsCRP) levels were also measured. At baseline, median (IQR) plasma 25OHD was 17 (13 to 22) ng/mL and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were: 1) total 25OHD: 3 (-3 to 8)%, 49 (30 to 82)%, and 69 (55 to 106)%, (P<0.001); 2) bioavailable 25OHD: 4 (-8 to 7)%, 45 (40 to 70)%, and 96 (58 to 136)%, (P<0.01); and 3) LL-37: -17 (-9 to -23)%, 4 (-10 to 14)%, and 30 (23 to 48)%, (P=0.04). Change in hsCRP levels did not differ between groups. A positive correlation was observed between bioavailable 25OHD and LL-37 (Spearman's rho=0.44, P=0.03), but not for total 25OHD and LL-37. Conclusions High-dose cholecalciferol supplementation rapidly and safely improves 25OHD and bioavailable 25OHD levels in patients with severe sepsis or septic shock. Changes in bioavailable 25OHD are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

152

160

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“…137 The repeated-exposure model has also been used for the study of sepsis-induced immunoparalysis, where IFN-γ treatment has partially reversed immune suppression and furthered pharmacologic interest for immunostimulation in sepsis. 138 Though these findings provide key initial insights into the elements of endotoxin tolerance, much research is still needed to elucidate the role of repeated LPS exposure on cardiometabolic physiology.…”

Section: Limitations and Challenges Of The Modelmentioning

confidence: 99%

Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases

Patel

Shah

Reilly³

2015

ATVB

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Inflammation is a fundamental feature of several complex cardiometabolic diseases. Indeed, obesity, insulin resistance, metabolic dyslipidemia, and atherosclerosis are all closely linked inflammatory states. Increasing evidence suggests that the infectious, biome-related or endogenous activation of the innate immune system may contribute to the development of metabolic syndrome and cardiovascular disease. Here we describe the human experimental endotoxemia model for the specific study of innate immunity in understanding further the pathogenesis of cardiometabolic disease. In a controlled, experimental setting, administration of an intravenous bolus of purified Escherichia coli endotoxin activates innate immunity in healthy human volunteers. During endotoxemia, changes emerge in glucose metabolism, lipoprotein composition, and lipoprotein functions that closely resemble those observed chronically in inflammatory cardiovascular disease risk states. In this review we describe the transient systemic inflammation and specific metabolic consequences that develop during human endotoxemia. Such a model provides a controlled induction of systemic inflammation, eliminates confounding, undermines reverse causation, and possesses unique potential as a starting point for genomic screening and testing of novel therapeutics for treatment of the inflammatory underpinning of cardiometabolic disease.

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“…Однако в литературе появились публикации с сообщением о повышении уровня ИФН-ɣ и при сепсисе у взрос-лых [23]. По мнению авторов, этот феномен связан с восстановлением функции макрофагов при так на-зываемом «сепсис-индуцированном иммунопарали-че» [24]. Однако не исключено, что рост показателя ИФН-ɣ в нашем случае связан с сопутствующей вну-триутробной вирусной инфекцией.…”

Section: перинатология и неонатологияunclassified

Proinflammatory cytokine profile in children with neonatal sepsis

Хаертынов¹,

Анохин²,

Rizvanov³

et al. 2017

Ross. vestn. perinatol. pediatr.

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Reversal of Immunoparalysis in HumansIn Vivo

Abstract: IFN-γ partially reverses immunoparalysis in vivo in humans. These results suggest that IFN-γ is a promising treatment option to reverse sepsis-induced immunoparalysis.

Cited by 203 publications

References 52 publications

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases

Proinflammatory cytokine profile in children with neonatal sepsis

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