Dose‐Related Inflammatory Effects of Intravenous Endotoxin in Humans: Evaluation of a New Clinical Lot of<i>Escherichia coli</i>O:113 Endotoxin

Suffredini, A. F.; Hd, Hochstein; Fg, McMahon

doi:10.1086/314717

Cited by 134 publications

(121 citation statements)

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“…It is not apparent why different results are obtained. However, the current study used different lots of E. coli, which might have implication [16]. In septic patients, plasma cGMP increases [31] and, in volunteers, NO inhalation increases plasma cGMP in a dose-dependent manner [32].…”

Section: Discussionmentioning

confidence: 94%

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Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers

Soop¹,

Sollevi²,

Weitzberg³

et al. 2003

Eur Respir J

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Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model.At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method. NO-free air was inhaled prior to exhalation against a resistance. NO in orally and nasally exhaled air and in rectal gas was investigated. Plasma nitrite, nitrate, and guanosine 39, 59-monophosphate (cGMP) and the events after diclophenac administration were also studied.Endotoxin infusion resulted in tachycardia and fever. An early increase in oral eNO concentration was observed and oral eNO decreased after diclophenac administration. NO exhaled nasally, NO in rectum gas and nitrite/nitrate levels remained unchanged over the study period. cGMP increased after 4 h.These findings suggest an early increase in nitric oxide production from the lungs, probably due to increased activity of the constitutive nitric oxide synthase upon endotoxin stimulation. In contrast, nitric oxide production in the upper airways, measured as nasally exhaled nitric oxide and nitric oxide in rectal gas, remained unchanged. Further studies will elucidate if exhaled nitric oxide is a valuable marker of sepsis-induced lung injury and if monitoring of treatment is possible. Eur Respir J 2003; 21: 594-599.

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Section: Discussionmentioning

confidence: 94%

“…Nitrite/nitrate and cGMP in plasma were also analysed. Healthy volunteers were exposed to 4 ng?kg -1 Escherichia coli endotoxin, a dose that induces a prominent inflammatory response without being hazardous to the subject [16].…”

mentioning

confidence: 99%

Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers

Soop¹,

Sollevi²,

Weitzberg³

et al. 2003

Eur Respir J

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“…The study was approved by the institutional review board of the Clinical Research Center, New Orleans, and reviewed by the institutional review board of the National Institute of Allergy and Infectious Diseases ( 28 ). Twelve healthy male volunteers aged 22-49 years underwent a complete history and physical examination prior to entering the study.…”

Section: Human Studiesmentioning

confidence: 99%

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Vaisar

Tang

Babenko

et al. 2015

Journal of Lipid Research

160

132

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Journal of Lipid Research Volume 56, 2015 1519have triggered intense interest in targeting HDL for therapeutic intervention. Several recent observations have cast doubt on the hypotheses that HDL-C levels relate to CAD risk in humans and that elevating HDL-C is therapeutic ( 3, 4 ). For example, genetic variations that alter levels of HDL-C do not always associate with CAD risk, and interventions that elevate HDL-C do not necessarily reduce cardiovascular events in humans with established CAD ( 5 ). Taken together, these observations indicate that HDL is complex and that simply quantifying HDL-C might be a poor way to assess HDL function ( 6, 7 ).The ability of HDL (or serum HDL, serum depleted of apoB-containing lipoproteins) to promote sterol effl ux from cultured macrophages incubated with radiolabeled cholesterol can vary markedly, despite similar levels of HDL-C and apoA-I ( 8 ). Therefore, HDL-C is not necessarily the major determinant of HDL's macrophage sterol effl ux capacity in this system. Importantly, the effl ux capacity of serum HDL is lower in individuals with prevalent CAD ( 9-11 ). A recent study of a large cohort, initially free of CAD, demonstrated that sterol effl ux associates strongly and negatively with the risk of future cardiac events ( 12 ). This association was strengthened by multivariate adjustment, suggesting that impaired HDL function affects incident cardiovascular risk by processes distinct from those involving HDL-C, LDL-cholesterol (LDL-C), and other traditional lipid risk factors. Together, these observations indicate that the sterol effl ux capacity of HDL might be a marker, and perhaps a mediator, of atherosclerotic Abstract Recent studies demonstrate that HDL's ability to promote cholesterol effl ux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol effl ux capacity during vascular disease are unclear. Infl ammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol effl ux capacity. We therefore tested the hypothesis that HDL's impaired effl ux capacity is mediated by specifi c changes of its protein cargo. Humans with acute infl ammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C effl ux capacity was signifi cantly impaired. Proteomic analyses demonstrated that HDL's cholesterol effl ux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute infl ammation caused a marked impairment of HDL-C effl ux capacity that correlated with a large increase in HDL SAA. In striking contrast, the effl ux capacity of mouse infl ammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the infl ammatory impairment of HDL-C effl ux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. -Vaisar, T

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“…The volunteers were premedicated with one double-strength trimethoprim/sulfamethoxazole tablet 12 h and 1 h before bronchoscopy. Subjects with a history of sulfa allergy were given two doses of oral amoxicillin (500 mg), separated by 8 h. At the time of the first bronchoscopy, 10 ml of saline was instilled into a lung subsegment (either the right middle lobe or lingula, followed by instillation of the test dose of reference LPS (O:113; National Institutes of Health, Bethesda, MD) (19,20) 4 ng/kg in 10 ml of saline into the contralateral lung. The subjects were randomized to left or right lungs for LPS or saline instillation.…”

Section: Model Of Lps-induced Pulmonary Inflammationmentioning

confidence: 99%

Peripheral Blood Neutrophil Activation Patterns Are Associated with Pulmonary Inflammatory Responses to Lipopolysaccharide in Humans

Abraham

Nick

Azam

et al. 2006

The Journal of Immunology

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Increased nuclear accumulation of NF-κB in LPS-stimulated peripheral blood neutrophils has been shown to be associated with more severe clinical course in patients with infection associated acute lung injury. Such observations suggest that differences in neutrophil response may contribute to the pulmonary inflammation induced by bacterial infection. To examine this question, we sequentially measured LPS-induced DNA binding of NF-κB in neutrophils collected from healthy humans on at least three occasions, each separated by at least 2 wk, and then determined pulmonary inflammatory responses after instillation of LPS into the lungs. Consistent patterns of peripheral blood neutrophil responses, as determined by LPS-induced NF-κB DNA binding, were present in volunteers, with a >80-fold difference between individuals in the mean area under the curve for NF-κB activation. The number of neutrophils recovered from bronchoalveolar lavage after exposure to pulmonary LPS was significantly correlated with NF-κB activation in peripheral blood neutrophils obtained over the pre-LPS exposure period (r = 0.65, p = 0.009). DNA binding of NF-κB in pulmonary neutrophils also was associated with the mean NF-κB area under the curve for LPS-stimulated peripheral blood neutrophils (r = 0.63, p = 0.01). Bronchoalveolar lavage levels of IL-6 and TNFRII were significantly correlated with peripheral blood neutrophil activation patterns (r = 0.75, p = 0.001 for IL-6; and r = 0.48, p = 0.049 for TNFRII. These results demonstrate that stable patterns in the response of peripheral blood neutrophils to LPS exist in the human population and correlate with inflammatory response following direct exposure to LPS in the lung.

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Dose‐Related Inflammatory Effects of Intravenous Endotoxin in Humans: Evaluation of a New Clinical Lot ofEscherichia coliO:113 Endotoxin

Cited by 134 publications

References 13 publications

Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers

Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Peripheral Blood Neutrophil Activation Patterns Are Associated with Pulmonary Inflammatory Responses to Lipopolysaccharide in Humans

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