Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation

Fullerton, James N.; Segre, Elisabetta; Maeyer, Roel P.H. De; Maini, Alexander A.; Gilroy, Derek W.

doi:10.3791/53913-v

Cited by 7 publications

(10 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, various LPS doses (0.06-4 ng kg À1 ) have been used to replicate different inflammation conditions in healthy volunteers. 25 With the limited dose range applied in our study (0.5-2 ng kg À1 ), exploring wider dose ranges and prolonged exposures of LPS in future studies could potentially help identify a nonlinearity and tolerance phenomena in the LPS exposure-response relationships. 10,26 In addition, complementary preclinical studies were more likely to characterize such relationships due to the higher flexibility in dose ranging in comparison to healthy volunteer studies.…”

Section: Discussionmentioning

confidence: 90%

“…This is likely due to the modest LPS exposure levels attained in this study. To date, various LPS doses (0.06–4 ng kg −1 ) have been used to replicate different inflammation conditions in healthy volunteers 25 . With the limited dose range applied in our study (0.5–2 ng kg −1 ), exploring wider dose ranges and prolonged exposures of LPS in future studies could potentially help identify a nonlinearity and tolerance phenomena in the LPS exposure–response relationships 10,26 .…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations

Liu

Aulin

Guo

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

Clinical studies in healthy volunteers challenged with lipopolysaccharide (LPS), a constituent of the cell wall of Gram‐negative bacteria, represent a key model to characterize the Toll‐like receptor 4 (TLR4)‐mediated inflammatory response. Here, we developed a mathematical modelling framework to quantitatively characterize the dynamics and inter‐individual variability of multiple inflammatory biomarkers in healthy volunteer LPS challenge studies. Data from previously reported LPS challenge studies were used, which included individual‐level time‐course data for tumour necrosis factor α (TNF‐α), interleukin 6 (IL‐6), interleukin 8 (IL‐8) and C‐reactive protein (CRP). A one‐compartment model with first‐order elimination was used to capture the LPS kinetics. The relationships between LPS and inflammatory markers was characterized using indirect response (IDR) models. Delay differential equations were applied to quantify the delays in biomarker response profiles. For LPS kinetics, our estimates of clearance and volume of distribution were 35.7 L h−1 and 6.35 L, respectively. Our model adequately captured the dynamics of multiple inflammatory biomarkers. The time delay for the secretion of TNF‐α, IL‐6 and IL‐8 were estimated to be 0.924, 1.46 and 1.48 h, respectively. A second IDR model was used to describe the induced changes of CRP in relation to IL‐6, with a delayed time of 4.2 h. The quantitative models developed in this study can be used to inform design of clinical LPS challenge studies and may help to translate preclinical LPS challenge studies to humans.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations

Liu

Aulin

Guo

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…In fact, there are few studies even in adults using naturally sick faces. Prior studies in adults created “sick” face stimuli by experimentally manipulating health (i.e., inducing inflammation to simulate an immune response similar to sickness; Axelsson et al, 2018; Fullerton et al, 2016; Schedlowski et al, 2014) by adding sores to the skin using photo editing (Bressan, 2021), and by asking actors to pose as if they are going to vomit (Widen et al, 2013). In these types of studies, adults generally rated faces manipulated to appear ill, compared to healthy faces, as sicker and more negative in expression.…”

Section: Development Of Children's Knowledge About Contagionmentioning

confidence: 99%

Infection detection in faces: Children's development of pathogen avoidance

Leung,

Zeng,

Maylott

et al. 2023

Child Development

View full text Add to dashboard Cite

This study examined the development of children's avoidance and recognition of sickness using face photos from people with natural, acute, contagious illness. In a U.S. sample of fifty‐seven 4‐ to 5‐year‐olds (46% male, 70% White), fifty‐two 8‐ to 9‐year‐olds (26% male, 62% White), and 51 adults (59% male, 61% White), children and adults avoided and recognized sick faces (ds ranged from 0.38 to 2.26). Both avoidance and recognition improved with age. Interestingly, 4‐ to 5‐year‐olds' avoidance of sick faces positively correlated with their recognition, suggesting stable individual differences in these emerging skills. Together, these findings are consistent with a hypothesized immature but functioning and flexible behavioral immune system emerging early in development. Characterizing children's sickness perception may help design interventions to improve health.

show abstract

“…Lipopolysaccharide (LPS) challenge in healthy individuals is a useful tool for studying human inflammation and the impact on physiological signals. 1 Endotoxin challenge with Gram-negative bacterial LPS is known to induce strong physiological changes in cardiovascular function including increased heart rate (HR) and decreased heart rate variability (HRV). [2][3][4][5] Inflammation is typically assessed through evaluation of biomarkers in blood or tissue samples, which is not feasible long-term in at-home settings.…”

Section: Introductionmentioning

confidence: 99%

“…The inflammatory response provides a unique window into health and disease. Lipopolysaccharide (LPS) challenge in healthy individuals is a useful tool for studying human inflammation and the impact on physiological signals 1 . Endotoxin challenge with Gram‐negative bacterial LPS is known to induce strong physiological changes in cardiovascular function including increased heart rate (HR) and decreased heart rate variability (HRV) 2–5 …”

Section: Introductionmentioning

confidence: 99%

Using a wearable patch to develop a digital monitoring biomarker of inflammation in response to LPS challenge

Avey,

Chatterjee,

Manyakov

et al. 2024

Clinical Translational Sci

View full text Add to dashboard Cite

Remote inflammation monitoring with digital health technologies (DHTs) would provide valuable information for both clinical research and care. Controlled perturbations of the immune system may reveal physiological signatures which could be used to develop a digital biomarker of inflammatory state. In this study, molecular and physiological profiling was performed following an in vivo lipopolysaccharide (LPS) challenge to develop a digital biomarker of inflammation. Ten healthy volunteers received an intravenous LPS challenge and were monitored for 24 h using the VitalConnect VitalPatch (VitalPatch). VitalPatch measurements included heart rate (HR), heart rate variability (HRV), respiratory rate (RR), and skin temperature (TEMP). Conventional episodic inpatient vital signs and serum proteins were measured pre‐ and post‐LPS challenge. The VitalPatch provided vital signs that were comparable to conventional methods for assessing HR, RR, and TEMP. A pronounced increase was observed in HR, RR, and TEMP as well as a decrease in HRV 1–4 h post‐LPS challenge. The ordering of participants by magnitude of inflammatory cytokine response 2 h post‐LPS challenge was consistent with ordering of participants by change from baseline in vital signs when measured by VitalPatch (r = 0.73) but not when measured by conventional methods (r = −0.04). A machine learning model trained on VitalPatch data predicted change from baseline in inflammatory protein response (R2 = 0.67). DHTs, such as VitalPatch, can improve upon existing episodic measurements of vital signs by enabling continuous sensing and have the potential for future use as tools to remotely monitor inflammation.

show abstract

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation

Cited by 7 publications

References 10 publications

Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations

Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations

Infection detection in faces: Children's development of pathogen avoidance

Using a wearable patch to develop a digital monitoring biomarker of inflammation in response to LPS challenge

Contact Info

Product

Resources

About