scholarly journals 233 NaturSafe® supplementation mitigates some aspects of the acute phase immune response to a lipopolysaccharide (LPS) challenge in weaned beef calves

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 117-117
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeffery A Carroll ◽  
Paul R Broadway ◽  
Tom S Edrington ◽  
Ilkyu Yoon ◽  
...  
Keyword(s):  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Serum Cortisol ◽  
Post Challenge ◽  
Serum Samples ◽  
Lps Challenge ◽  
Time Interaction ◽  
Tnf Α ◽  
Monitoring Devices

Abstract This study was conducted to determine if feeding calves NaturSafe would reduce the acute phase response (APR) to lipopolysaccharide (LPS) challenge. Crossbred steers (n=32; 274±2 kg) were randomly allotted to two treatment diets: 1) Control, fed a standard receiving ration, and 2) NaturSafe, fed the Control ration supplemented with NaturSafe at 12 g/hd/d (NaturSafe®, Diamond V). On d22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual stalls. On d23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Serum samples were collected and sickness behavior scores (SBS) recorded at 0.5-h intervals from -2 to 8h and at 24h relative to LPS challenge. Rectal temperatures were greater (P=0.01) in NaturSafe compared to Control steers for the following time intervals following LPS challenge: 6 to 11h, 13h, 15 to 20h, and 22 to 24h. Additionally, SBS were reduced (P< 0.01) in NaturSafe compared to Control steers. White blood cell concentrations were greater (P=0.05) in NaturSafe compared to Control steers prior to the LPS challenge, yet the response to LPS did not differ between treatments (P >0.05). A treatment × time interaction for serum cortisol concentrations (P< 0.01) showed an increase at 0.5 and 2h post-challenge but a reduction at 3h in NaturSafe compared to Control steers. Additionally, fibrinogen was greater (P< 0.01) in NaturSafe compared to Control steers. There was a treatment × time interaction (P< 0.01) for TNF-α where concentrations were reduced from 1 to 2h post-challenge in NaturSafe compared to Control steers. Serum IL-6 tended (P=0.09) to show a reduction in serum concentrations in NaturSafe compared to Control steers. There was a tendency (P=0.07) for a treatment × time interaction for IFN-γ. Overall these data suggest a priming effect of NaturSafe on the innate immune system of steers, resulting in an attenuated APR to the LPS challenge.

scholarly journals Prenatal immune stimulation alters the postnatal acute phase and metabolic responses to an endotoxin challenge in weaned beef heifers,

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Jeffery A Carroll ◽  
Nicole C Burdick Sanchez ◽  
Paul R Broadway ◽  
Gleise M Silva ◽  
Juliana Ranches ◽  
...  
Keyword(s):  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Metabolic Responses ◽  
Immune Stimulation ◽  
Endotoxin Challenge ◽  
Lps Challenge ◽  
Time Interaction ◽  
Tnf Α ◽  
Immunological Effects

Abstract This study evaluated whether administration of lipopolysaccharide (LPS) at each trimester of gestation would alter the acute phase (APR) and metabolic responses to a postnatal LPS challenge in weaned heifers. Pregnant crossbred multiparous cows (n = 50) were randomized into prenatal immune stimulation (PIS; n = 24; administered 0.1 µg/kg BW LPS subcutaneously at 71 ± 2, 170 ± 2 and 234 ± 2 d of gestation) and saline (CON; n = 26) groups. From these treatment groups, heifer calves (n = 12 PIS and 11 CON) were identified at weaning (244 ± 3 d of age) to receive an LPS challenge. On d 0, heifers were fitted with vaginal temperature (VT) devices, jugular catheters, and moved into individual stalls. On d 1, heifers were challenged i.v. with LPS (0.5 µg/kg BW) at 0 h. Blood samples were collected and sickness behavior scores (SBS) recorded at 0.5 h intervals from −2 to 8 h and at 24 h relative to LPS challenge. Serum was analyzed for cortisol, cytokines, glucose, non-esterified fatty acids (NEFA), and serum urea nitrogen (SUN) concentrations. Baseline VT was lesser in PIS heifers from −11 to −5 h pre-LPS (treatment × time: P < 0.01) compared to the CON; however, the post-LPS VT response did not differ between treatments (P = 0.89). There was a treatment × time interaction (P < 0.01) for SBS with PIS heifers having lesser SBS from 0.5 to 2 h post-LPS compared to CON. There was a treatment × time interaction (P = 0.03) for cortisol with PIS heifers having greater cortisol at 0.5, 3, 3.5, 5.5 and 6.5 h post-LPS compared to CON. There were treatment × time interactions for the post-LPS cytokine responses (P ≤ 0.05). Specifically, PIS heifers had greater TNF-α from 1.5 to 2 h, yet less TNF-α at 3 h than CON (P < 0.01), and PIS heifers had greater IFN-γ from 3.5 to 5.5 h post-LPS than CON (P < 0.01). In contrast, IL-6 was less in PIS than CON heifers from 1.5 to 8 h post-LPS (P < 0.001). Glucose concentrations were greater in PIS heifers at −1 h, but less at 2, 3 and 5.5 h compared to CON (treatment × time: P < 0.01). Serum NEFA concentrations were greater (P = 0.04) in PIS than CON heifers. There was a treatment × time interaction (P < 0.01) for SUN with PIS heifers having greater SUN concentrations at −2, −1.5, 2, 3, 6.5 and 24 h than CON. These data demonstrate that in utero exposure to multiple low doses of endotoxin has lasting physiological and immunological effects when the offspring encounter a similar postnatal immunological insult.

scholarly journals Some aspects of the acute phase immune response to a lipopolysaccharide (LPS) challenge are mitigated by supplementation with a Saccharomyces cerevisiae fermentation product in weaned beef calves1,2

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeff A Carroll ◽  
P Rand Broadway ◽  
Tom S Edrington ◽  
Ilkyu Yoon ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Immune Response ◽  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Lps Challenge ◽  
Time Interaction ◽  
Fermentation Product ◽  
Tnf Α ◽  
Saccharomyces Cerevisiae Fermentation Product

Abstract This study was conducted to determine if feeding a Saccharomyces cerevisiae fermentation product (SCFP) to calves would alter the acute phase response to a lipopolysaccharide (LPS) challenge. Crossbred steer calves [n = 32; 274 ± 1.9 kg body weight (BW)] were randomly allotted to two treatment diets for 21 d: 1) control, fed RAMP (Cargill, Dalhart, TX) and 2) SCFP, fed the control ration supplemented with NaturSafe at 12 g/hd/d mixed into the TMR (NaturSafe, Diamond V, Cedar Rapids, IA). On day 22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual bleeding stalls. On day 23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Blood samples were collected at 0.5-h (serum) or 2-h (complete blood counts) intervals from −2 to 8 h and again at 24 h relative to the LPS challenge at 0 h. Sickness behavior scores (SBS) were recorded after the collection of each blood sample. Rectal temperatures were greater in SCFP steers from 6 to 11 h, at 13 h, from 15 to 20 h, and from 22 to 24 h following the LPS challenge compared to Control steers (treatment × time: P = 0.01). Additionally, SCFP-supplemented steers had reduced (P < 0.01) SBS compared to Control steers. Platelet concentrations remained greater in SCFP-supplemented steers compared to Control steers throughout the study (P = 0.05), while there was a tendency (P = 0.09) for SCFP steers to have greater white blood cells and eosinophils concentrations than Control steers. There was a treatment × time interaction for serum cortisol and glucose (P < 0.01). Specifically, cortisol was greater at 0.5 and 2 h postchallenge but was reduced at 3 h for SCFP steers compared to Control steers. Glucose was greater in SCFP steers at −0.5, 2, and 7.5 h compared to Control steers. Serum amyloid A was reduced in SCFP steers at 0.5 h, yet greater at 1 and 7.5 h postchallenge compared to Control steers (treatment × time: P < 0.01). Fibrinogen concentrations were greater (P < 0.01) in SCFP compared to Control steers. There was a treatment × time interaction (P < 0.01) for tumor necrosis factor-α (TNF-α) such that concentrations were reduced in SCFP steers from 1 to 2 h postchallenge compared to Control steers. Overall, these data suggest that supplementing calves with SCFP may have primed the innate immune response prior to the challenge, particularly platelets, which resulted in an attenuated sickness behavior and TNF-α response to LPS.

scholarly journals In utero exposure to LPS alters the postnatal acute-phase response in beef heifers

2016 ◽  
Vol 23 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Jeffery A Carroll ◽  
Nicole C Burdick Sanchez ◽  
John D Arthingon ◽  
Corwin D Nelson ◽  
Aimee L Benjamin ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Potential Effect ◽  
Phase Response ◽  
In Utero Exposure ◽  
Lps Challenge ◽  
Time Interaction ◽  
Vaginal Temperature

The potential effect of prenatal LPS exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers was determined. Pregnant crossbred cows were separated into prenatal immune stimulation (PIS) and saline groups (Control). From these treatments, heifer calves were identified at weaning to subsequently receive an exogenous LPS challenge. Sickness behavior scores (SBS) were recorded and blood samples were collected at 30-min intervals from −2 to 8 h and again at 24 h relative to the LPS challenge. There was a treatment × time interaction for the change in vaginal temperature (VT) such that the change in VT was greater in Control than PIS from 150 to 250 min, yet it was greater in PIS than Control from 355 to 440 min and from 570 to 1145 min. There was also a treatment × time interaction for SBS such that scores were greater in Control than PIS at 0.5 h, yet were greater in PIS than Control from 2.5 to 4 h post-LPS. There was a tendency for a treatment × time interaction for serum concentrations of IL-6, which were greater in PIS than Control heifers from 5.5 to 6 h and from 7 to 8 h post-challenge. Thus, a single exposure to LPS during gestation can alter the postnatal APR to LPS in heifer calves.

scholarly journals 2 Acute phase response to lipopolysaccharide challenge in beef steers supplemented with prebiotic blends

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 38-39
Author(s):  
Nicole C Burdick Sanchez ◽  
Paul R Broadway ◽  
Jeffery A Carroll ◽  
Devan M Paulus Compart ◽  
J C Forcherio
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Sickness Behavior ◽  
Serum Cortisol ◽  
Phase Response ◽  
Energy Utilization ◽  
Beef Steers ◽  
Lps Challenge ◽  
Complete Blood Counts ◽  
Metabolic Biomarkers

Abstract A study was conducted to determine the effects of two prebiotic blends on the acute phase response (APR) following lipopolysaccharide (LPS) challenge in steers. Crossbred steers (n = 36; 273±4 kg) were fed for 21d on three different treatments: 1) Control, fed a standard receiving ration; 2) Control ration supplemented with a Prebiotic/Probiotic blend (28.4 g/hd/d; PMI); and 3) Control ration supplemented with a DFM/Prebiotic blend (19.0 g/hd/d; PMI). On d20, calves were fitted with indwelling rectal temperature (RT) monitors and jugular catheters and moved into individual stanchions in a covered barn. On d21, blood samples were collected, and sickness behavior scores recorded at 0.5-h intervals from -2 to 8h and again at 24h relative to an i.v. challenge with 0.25 µg/kg BW LPS. Serum was isolated and stored until analyzed for pro-inflammatory cytokines, cortisol and glucose concentrations. Complete blood counts were measured every 2h from -2 to 8h and again at 24h. Pre-challenge RT measured for 18h prior to the challenge tended (P = 0.10) to be affected by treatment such that calves fed the Prebiotic/Probiotic blend had greater RT than Control and tended to be greater than calves fed the DFM/Prebiotic blend (38.9, 39.2, and 39.0±0.1oC, respectively). Post-challenge RT increased 0.8–1.0oC on average but did not differ between treatments (P = 0.53). Sickness behavior scores were not different between treatments (P = 0.14). There were no differences in white blood cell or differential counts between treatments (P ≥ 0.25). Serum concentrations of TNF-α, IL-6, and IFN-γ increased in response to the challenge (P < 0.01) but were not different between treatments (P ≥ 0.26). Serum cortisol and glucose concentrations were reduced in both supplemented groups compared to Control steers (P ≤ 0.006). Therefore, the data suggest that the effects of the prebiotic blends during an immune challenge were limited to alterations in metabolic biomarkers and energy utilization.

scholarly journals Supplementation of OmniGen-AF improves the metabolic response to a glucose tolerance test in beef heifers1,2

2019 ◽  
Vol 3 (4) ◽  
pp. 1521-1529
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeffery A Carroll ◽  
Paul R Broadway ◽  
Tyler H Schell ◽  
Steve B Puntenney ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Treatment Time ◽  
Metabolic Response ◽  
Control Diet ◽  
Tolerance Test ◽  
Blood Collection ◽  
Post Challenge ◽  
Time Interaction ◽  
Post Infusion

Abstract: This study determined whether feeding the immunomodulating supplement, OmniGen-AF, to feedlot heifers would alter metabolic profiles to a glucose tolerance test. Heifer calves (n = 32; 217 ± 2 kg) were allocated into two treatment diets: 1) Control, fed a standard receiving ration, and 2) OmniGen, fed the Control diet supplemented with OmniGen at 4.54 g/45 kg BW/d. Heifers were fed for 42 d. On d 42, Heifers were processed through a working facility for placement of indwelling jugular catheters. After these procedures, heifers were moved into individual stanchions in an enclosed barn and all heifers were fed their treatment diets at 1400 h. All orts were removed at 2000 h to allow for a 12-h fast prior to first blood collection. The following day, heifers were administered 0.5 mL/kg BW of a 50% dextrose solution at 0900 h (0 min). Blood samples were collected for serum isolation at −60, −45, −30, −15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to bolus dextrose infusion. Serum was stored at −80 oC until analyzed for cortisol, glucose, insulin, non-esterified fatty acid (NEFA) and urea N concentrations. There was a treatment × time interaction for post-challenge cortisol (P = 0.004) such that cortisol was greater in OmniGen heifers than Control heifers from 10- to 45- min post-infusion. Glucose concentrations increased post-infusion (P < 0.01) and were reduced in OmniGen compared to Control heifers at 10-, 45-, and 90-min after challenge (treatment × time P < 0.001). Similarly, there was a treatment × time interaction for post-challenge insulin concentrations (P = 0.04) such that insulin was greater in OmniGen-fed heifers than Control heifers from 10 to 30 min. In addition, there was a treatment × time interaction (P = 0.01) for NEFA concentrations such that concentrations were reduced in OmniGen-supplemented heifers from 10 to 30 min following administration of the dextrose bolus. Serum urea N concentrations were greater in Control heifers at 150 min compared to OmniGen-fed heifers (post-challenge treatment × time interaction: P < 0.001). These data suggest that OmniGen-fed heifers were more responsive to changes in glucose, perhaps affecting the storage and/or redistribution of energy deposits and provide further evidence for altered metabolism in OmniGen-supplemented cattle. The differences observed may explain differences observed in the immune response in OmniGen-supplemented calves.

scholarly journals The dose response of inhaled LPS challenge in healthy subjects

2018 ◽  
Vol 16 ◽  
pp. 205873921878482 ◽  
Author(s):  
Alex Mulvanny ◽  
Natalie Jackson ◽  
Caroline Pattwell ◽  
Sophie Wolosianka ◽  
Thomas Southworth ◽  
...  
Keyword(s):  
Dose Response ◽  
Good Manufacturing Practice ◽  
Post Challenge ◽  
Reactive Protein ◽  
Lps Challenge ◽  
Cell Counts ◽  
Neutrophil Percentage ◽  
Tnf Α ◽  
Factor Α ◽  
Serum Crp

Lipopolysaccharide (LPS) inhalation causes neutrophilic airway inflammation. We used LPS produced to Good Manufacturing Practice (GMP) standards to characterise the dose response. A total of 15 healthy non-smoking subjects inhaled 5-, 15- and 50-µg LPS. Whole blood cell counts and serum C-reactive protein (CRP) were measured at baseline and up to 24 h post challenge. Sputum was induced at baseline and 6 h post challenge for cell counts and quantification of myeloperoxidase (MPO), interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor α (TNF-α) in supernatants. LPS inhalation was well tolerated. Blood neutrophil counts increased at 6 h post LPS with all doses. Serum CRP significantly increased with 15- and 50-µg LPS. All LPS doses significantly increased sputum neutrophil percentage ( P < 0.001). IL-1β, IL-6 and TNF-α were significantly increased in sputum supernatant following challenge with 50-µg LPS, there was no change in MPO or IL-8. The 50-µg LPS was well tolerated and produced a robust inflammatory response. This study supports the use of 50-µg GMP-grade LPS as a suitable challenge agent in clinical trials.

scholarly journals 185 Impact of hydroxy-selenomethionine supplementation during late gestation and lactation in sows on piglet immunocompetence

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 107-107
Author(s):  
Ningya Li ◽  
Zhijian Sun ◽  
Niel A Karrow ◽  
Mickael Briens ◽  
Michele De Marco ◽  
...  
Keyword(s):  
Immune Status ◽  
Late Gestation ◽  
Post Challenge ◽  
Serum Samples ◽  
E Coli ◽  
Egg White Lysozyme ◽  
Lps Challenge ◽  
Pregnancy And Lactation ◽  
Specific Igg ◽  
Dietary Treatments

Abstract The benefits of selenium (Se) supplementation during pregnancy and lactation in sows on piglet immunocompetence are not yet fully understood. This study aimed to assess piglet immune status when sows were fed Se-deficient or supplemented diets with sodium selenite (SS) or hydroxy-selenomethionine (OH-SeMet). Twelve pregnant sows were randomly assigned to 3 dietary treatments (4 sows each): no supplemental Se (NC), SS at 0.3 mg Se/kg (SS-0.3), OH-SeMet at 0.3 mg Se/kg (SO-0.3). The trial was carried out from gestation day (gd) 84 to weaning on postpartum day (ppd) 21, at which time all the piglets received the same diet having as Se source SS. On gd 98 and 105, sows were vaccinated with hen egg white lysozyme (HEWL). On ppd 0 and 21, 8 piglets/treatment were euthanized to obtain blood and muscle samples for total Se analyses. Serum samples were collected from 8 female piglets/treatment on ppd 0 and 2 to assess antigen-specific antibody titer for HEWL. On ppd 23, 6 weaned female piglets/treatment were intramuscular challenged with E. coli lipopolysaccharide (LPS) and serum IL-10 levels were measured at 24 h pre-challenge and at 2 and 48 h post challenge. At day 21, piglets from sows fed SO-0.3 showed the highest muscle Se deposition (P < 0.001). At ppd 0, no difference for HEWL-specific IgG was found while at ppd 2, SO-0.3 showed the highest HEWL-specific IgG concentration (P < 0.05). At 24 h pre-challenge and 2 h post LPS challenge, SO-0.3 showed a greater IL-10 level as compare to NC and SS-0.3, respectively (P < 0.05); no difference was found for the same parameter at 48 h post challenge. Piglets from SO supplemented sows exhibited stronger early immune response to LPS challenge. This study indicates the importance of sow Se supplementation with a pure organic form of Se such as OH-SeMet to enhance piglets Se and immune status.

Pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs

2006 ◽  
Vol 82 (4) ◽  
pp. 527-534 ◽  
Author(s):  
S. Llamas Moya ◽  
L. Boyle ◽  
P. B. Lynch ◽  
S. Arkins
Keyword(s):  
Gender Differences ◽  
Acute Phase ◽  
Inflammatory Cytokine ◽  
Low Dose ◽  
Acute Phase Protein ◽  
Plasma Concentrations ◽  
Lps Challenge ◽  
Tnf Α ◽  
Phase Protein ◽  
Pro Inflammatory Cytokines

AbstractThe objective of this study was to establish the pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs and to determine whether these immune parameters could also be measured in saliva. Possible gender differences in the acute phase reaction were also assessed. At 6 weeks of age, 24 male and 24 female pigs were injected intraperitoneally with a single dose of 0 or 5 μg/kg live weight (LW) of LPS fromEscherichia coli(treatment). Matched saliva and blood samples were taken at 0, 2, 4, 8, 12 or 24 h after treatment administration. Samples were analysed for concentrations of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), the acute phase proteins C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), and cortisol. Low-dose LPS administration increased plasma levels of TNF-α (P<0·001), CRP (P<0·05) and SAA (P<0·05) but did not affect plasma concentrations of IL-1β or Hp (P>0·1). Treatment by time interactions showed that plasma levels of TNF-α and CRP in LPS-treated pigs peaked at 2 h (P<0·001) and 12 h (P<0·01), respectively. Low-dose LPS injection tended to increase plasma concentrations of cortisol (P=0·056) and the response to LPS differed between genders (P<0·05), with females showing higher cortisol responsiveness to the challenge (P<0·01). Males showed higher levels of both cytokines regardless of the treatment (P<0·05), probably due to the inhibition of cytokine synthesis by cortisol. Concentrations of both pro-inflammatory cytokines were consistently detectable in saliva and were present in higher concentrations than in plasma (P<0·001). Hence, plasma TNF-α, CRP and SAA are useful indicators of sub-acute inflammation/infection in pigs as simulated by a low-dose LPS challenge and gender differences exist in the pro-inflammatory cytokine response after a low dose of LPS.

scholarly journals PSIII-38 Butyric acid and derivatives: In vitro anti-inflammatory effects tested in porcine alveolar macrophages

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 370-370
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Organic Acid ◽  
Butyric Acid ◽  
Sodium Butyrate ◽  
Alveolar Macrophages ◽  
Block Design ◽  
Lps Challenge ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Challenge Group

Abstract The aim of this experiment was to examine the anti-inflammatory effects of butyric acid, sodium butyrate, monobutyrin and tributyrin using porcine alveolar macrophages (PAMs). PAMs were isolated from the bronchial lavage of 6 piglets at 6 weeks of age, and then seeded at 106 cells/mL in 24-well plates. After 24 h incubation, cells were treated with different treatments in a randomized complete block design with 10 replicates. The treatments were in a factorial arrangement with 2 doses of lipopolysaccharide (LPS, 0 or 1 μg/mL) and 5 levels of organic acid (0, 0.5, 1, 2, 4 mM for butyric acid and tributyrin and 0, 1, 2, 4, 8 mM for sodium butyrate and monobutyrin). Supernatants were collected after another 24 h incubation and analyzed for tumor necrosis factor alpha (TNF-α). Cell viability was also tested by the MTT assay. Data were analyzed using the MIXED procedure of SAS. No cytotoxic effect was observed in LPS challenge and each organic acid with the percentage of live cells was more than 76% in comparison to the sham control. Sodium butyrate at 2 and 4 mM dose exhibited (P &lt; 0.01) a stimulatory effect on cell proliferation. LPS challenge remarkably stimulated (P &lt; 0.0001) TNF-α secretion from PAMs. In the non-challenge group, butyric acid, monobutyrin, and tributyrin linearly reduced TNF-α production from PAMs, whereas 2 mM sodium butyrate tended to increase (P = 0.056) TNF-α secretion from PAMs. In the LPS challenge group, all tested organic acid dose-dependently reduced (P &lt; 0.001) TNF-α production from LPS-challenged PAMs, with the strongest inhibiting effect observed at the highest dose. Results indicated that butyric acid and its derivatives that were tested in the current experiment all had strong anti-inflammatory activities in vitro.

scholarly journals GMP-compliant fully automated radiosynthesis of [18F]FEPPA for PET/MRI imaging of regional brain TSPO expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Wei Chang ◽  
Chuang-Hsin Chiu ◽  
Ming-Hsien Lin ◽  
Hung-Ming Wu ◽  
Tsung-Hsun Yu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Western Blotting ◽  
Second Generation ◽  
Mrna Levels ◽  
Automated Radiosynthesis ◽  
Lps Challenge ◽  
Tnf Α ◽  
The Brain ◽  
Tspo Expression

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. Conclusions Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO.

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