In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs

Wyns, Heidi; Plessers, Elke; Backer, Patrick De; Meyer, Evelyne; Croubels, Siska

doi:10.1016/j.vetimm.2015.06.001

Cited by 92 publications

(63 citation statements)

References 119 publications

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“…During the experiment, we sampled plasma over time for monitoring of cytokine release. We found significant increases in TNF-␣ and IL-10 after 120 min and significant increases in IL-6, -8, -12, and -1␤ after 180 min in all 7 animals who received LPS and developed ARDS, which is similar to cytokine profiles in other porcine models of ALI and ARDS (12). Importantly, the rapid and massive increases of TNF-␣, IL1-␤, IL-6, IL-8, and IL-10 that were observed in our model have been shown to be linked to mortality in ARDS patients (9).…”

Section: Discussionsupporting

confidence: 75%

Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Stenlo

Hyllén

Silva

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Acute respiratory distress syndrome (ARDS) is a common cause of death in the intensive care unit, with mortality rates of~30 -40%. To reduce invasive diagnostics such as bronchoalveolar lavage and time-consuming in-hospital transports for imaging diagnostics, we hypothesized that particle flow rate (PFR) pattern from the airways could be an early detection method and contribute to improving diagnostics and optimizing personalized therapies. Porcine models were ventilated mechanically. Lipopolysaccharide (LPS) was administered endotracheally and in the pulmonary artery to induce ARDS. PFR was measured using a customized particles in exhaled air (PExA 2.0) device. In contrast to control animals undergoing mechanical ventilation and receiving saline administration, animals who received LPS developed ARDS according to clinical guidelines and histologic assessment. Plasma levels of TNF-␣ and IL-6 increased significantly compared with baseline after 120 and 180 min, respectively. On the other hand, the PFR significantly increased and peaked 60 min after LPS administration, i.e.,~30 min before any ARDS stage was observed with other well-established outcome measurements such as hypoxemia, increased inspiratory pressure, and lower tidal volumes or plasma cytokine levels. The present results imply that PFR could be used to detect early biomarkers or as a clinical indicator for the onset of ARDS.

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Section: Discussionsupporting

confidence: 75%

Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Stenlo

Hyllén

Silva

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Under inflammatory conditions acute immune response is followed by the synthesis and release of different APP, including C-reactive protein, haptoglobulin, alkaline phosphatase and pigMAP [42]. Although their exact physiological actions have not been entirely elucidated, APP seem to control inflammatory response [43].…”

Section: Discussionmentioning

confidence: 99%

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota

Liehr

Mereu²,

Pastor³

et al. 2017

PLoS ONE

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Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function.

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“…Lipopolysaccharide (LPS), a structural part of the outer membrane of Gram-negative bacteria, is one of the most effective stimulators of the immune system and has been widely used in pigs as an experimental model for bacterial infections (Wyns, Plessers, De Backer, Meyer, & Croubels, 2015).…”

Section: Introductionmentioning

confidence: 99%

Effects of chitosan nanoparticle supplementation on growth performance, humoral immunity, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs

Mao

Yang

et al. 2019

Animal Physiology Nutrition

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In this study, we aimed to determine the effects of dietary supplementation with chitosan nanoparticles (CNP) on growth performance, immune status, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs. A total of 144 piglets were assigned to four groups receiving different dietary treatments, including basal diets supplemented with 0, 100, 200 and 400 mg/kg CNP fed for 28 days. Each treatment group included six pens (six piglets per pen). The increase in supplemental CNP concentration improved the average daily gain (ADG) and decreased the feed and gain (F/G) and diarrhoea rate (p < .05). However, significant differences in the average daily feed intake (ADFI) among different CNP concentrations were not observed. CNP also increased plasma immunoglobulin (Ig)A and IgG, and C3 and C4 concentrations in piglets in a dose‐dependent manner on day 28, whereas IgM concentration was not affected by CNP. A total of 24 piglets in the control diet and control diet with 400 mg/kg CNP supplementation groups were randomly selected for the experiment of immunological stress. Half of the pigs in each group (n = 6) were injected i.p. with Escherichia coli lipopolysaccharide (LPS) at a concentration of 100 μg/kg. The other pigs in each group were injected with sterile saline solution at the same volume. Plasma concentrations of cortisol, prostaglandin E2 (PEG2), interleukin (IL)‐6, tumour necrosis factor (TNF)‐α and IL‐1β dramatically increased after LPS challenge. However, CNP inhibited the increase in cortisol, PEG2, IL‐6 and IL‐1β levels in plasma, whereas TNF‐α level slightly increased. Moreover, the effects of CNP on the gut microbiota were also evaluated. Our results showed that dietary supplementation with CNP modified the composition of colonic microbiota, where it increased the amounts of some presumably beneficial intestinal bacteria and suppressed the growth of potential bacterial pathogens. These findings suggested CNP supplementation improved the growth performance and immune status, alleviated immunological stress and regulated intestinal ecology in weaned piglets. Based on these beneficial effects, CNP could be applied as a functional feed additives supplemented in piglets diet.

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In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs

Cited by 92 publications

References 119 publications

Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota

Effects of chitosan nanoparticle supplementation on growth performance, humoral immunity, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs

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