Effect Of Acute Inflammation Research Articles

The bronchoalveolar lavage dilution conundrum: an updated view on a long-standing problem.

Bronchoalveolar lavage (BAL) is used by researchers to study molecular interactions within healthy and diseased human lungs. However, the utility of BAL fluid measurements may be limited by difficulties accounting for dilution of the epithelial lining fluid (ELF) sampled and inconsistent collection techniques. The use of endogenous markers to estimate ELF dilution has been proposed as a potential method to normalize acellular molecule measurements in BAL fluid, but these markers are also imperfect and prone to inaccuracy. The focus of this report is to review factors that affect the interpretation of acellular molecule measurements in lung ELF and present original data comparing the performance of several BAL dilution markers during health and in a human endobronchial endotoxin challenge model of acute inflammation. Our findings suggest that incomplete ELF and lavage fluid mixing, flux of markers across the alveolar barrier, and lung inflammation are all possible factors that can affect marker performance. Accounting for these factors, we show that commonly used markers including urea, total protein, albumin, and immunoglobulin M are likely unreliable BAL dilution markers. In contrast, surfactant protein D appears to be less affected by these factors and may be a more accurate and biologically plausible marker to improve the reproducibility of acellular BAL component measurements across individuals during health and inflammatory states.NEW & NOTEWORTHY In this report, mathematical prediction models and real-world measurements are used to compare the performance of molecular markers of dilution in bronchoalveolar lavage fluid samples. Effects of acute inflammation within individual subjects are highlighted. These findings inform recommendations for normalizing measurements across bronchoalveolar lavage samples and highlight the need for additional markers to improve the rigor of translational studies utilizing bronchoalveolar lavage measurements.

Polysaccharide-rich extract of Genipa americana leaves exerts anti-inflammatory effects modulated by platelet mediators

Ethnopharmacological relevanceGenipa americana L. (Rubiaceae) leaves are traditionally used to treat fever, pharyngitis, healing, luxation and bruises. Aim of the studyThis study aimed to investigate the anti-inflammatory effect of the polysaccharide-rich extract of G. americana leaves (PE-Ga) in acute inflammation models and underlying mechanisms associated with platelet activity. Materials and methodsRats received PE-Ga (0.3–3.0 mg/kg; IV) 30 min before injection (IP or SC) of zymosan, serotonin, PGE2, PLA2, PAF or L-arginine, and evaluated in the models of paw edema and acute peritonits. The blockage of plasma serotonin reuptake into platelets was performed with fluoxetine (40 mg/kg; IP). ResultsIn vitro, PE-Ga inhibited ADP-induced platelet aggregation up to 49%. In the edema model, PE-Ga reduced (41%) the time-course of the edema induced by zymosan, mainly the last phase (62%), as well as that induced by PLA2 (32%), PAF (35%), L-arginine (36%), PGE2 (49%) or serotonin (54% AUC); and reversed paw hypernociception induced by PGE2 or serotonin. In the peritonitis model, PE-Ga reversed abdominal hypernociception and reduced leukocyte migration induced by zymosan to blood (38%) and peritoneal cavity (55%), mainly neutrophils (70%). PE-GA also decreased leukocyte rolling (32%) and adhesion (47%), and increased the rolling velocity 2.2-fold. In the peritoneal fluid, PE-Ga reversed P-selectin and reduced total proteins (17%), MDA (40%), NO2−/NO3− (27%), and MPO activity (43%) but increased catalase activity 3.3-fold compared to zymosan. In addition, fluoxetine reversed PE-Ga anti-inflammatory effect on leukocyte migration and adhesion. ConclusionsPE-Ga exerts antiplatelet and anti-inflammatory effects in acute inflammation induced by zymosan, being modulated by P-selectin and platelet serotonin, among other inflammatory mediators.

Effects of acute inflammation on platelet indices: An experimental study

Background and objective: It is well known that inflammation may affect the platelets. However, there are inconsistencies between the results of observational studies investigating changes in platelet indices in inflammatory conditions. This study aimed to investigate the possible effects of acute inflammation on platelet indices in plantar inflammation model in rats. Methods: A total of 20 rats, 10 in each group, were used in the study. Lambda-carrageenan and saline were applied subcutaneously to the right hind paw of the rats in the inflammation group and in the control group, respectively. Six hours after the administration, blood samples were taken from femoral arteries and femoral veins, and platelet indices were measured by a hematology analyzer. In addition, plantar tissue samples belonging to the control and inflammation groups were evaluated histopathologically. Results: On histopathological examination, no pathological condition was observed in the control group, while there were changes consistent with acute inflammation in the lambda-carrageenan-injected group. There was no significant difference in terms of platelet indices between both the arterial and vein samples and between the control and inflammation groups. Conclusions: Our results suggest that platelet indices cannot be used in the diagnosis of acute inflammatory conditions. However, in our opinion, these findings must not be interpreted as that acute inflammation does not affect platelet number and volume. Instead, we believe that it may be more appropriate to say that acute inflammation does not produce a quantitatively significant change in platelet indices due to the combination of the opposite effects.

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation.

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

Oral vitamin C restores endothelial function during acute inflammation in young and older adults.

Oxidative stress has been linked to reductions in vascular function during acute inflammation in young adults; however, the effect of acute inflammation on vascular function with aging is inconclusive. The aim of this study was to determine if oral antioxidant administration eliminates vascular dysfunction during acute inflammation in young and older adults. Brachial flow‐mediated dilation (FMD) and carotid‐femoral pulse wave velocity (PWV) were measured in nine young (3 male, 24 ± 4 yrs, 26.2 ± 4.9 kg/m2) and 16 older (13 male, 64 ± 5 yrs, 25.8 ± 3.2 kg/m2) adults before and 2‐h after oral consumption of 2 g of vitamin C. The vitamin C protocol was completed at rest and 24 h after acute inflammation was induced via the typhoid vaccine. Venous blood samples were taken to measure markers of inflammation and vitamin C. Both interleukin‐6 (Δ+0.7 ± 1.8 pg/ml) and C‐reactive protein (Δ+1.9 ± 3.1 mg/L) were increased at 24 h following the vaccine (p < 0.01). There was no change in FMD or PWV following vitamin C administration at rest (p > 0.05). FMD was lower in all groups during acute inflammation (Δ‐1.4 ± 1.9%, p < 0.01), with no changes in PWV (Δ‐0.0 ± 0.9 m/s, p > 0.05). Vitamin C restored FMD back to initial values in young and older adults during acute inflammation (Δ+1.0 ± 1.8%, p < 0.01) with no change in inflammatory markers or PWV (p > 0.05). In conclusion, oral vitamin C restored endothelial function during acute inflammation in young and older adults, with no effect on aortic stiffness. The effect of vitamin C on endothelial function did not appear to be due to reductions in inflammatory markers. The exact mechanisms should be further investigated.

Inhibition of vascular adhesion protein 1 protects dopamine neurons from the effects of acute inflammation and restores habit learning in the striatum

BackgroundChanges in dopaminergic neural function can be induced by an acute inflammatory state that, by altering the integrity of the neurovasculature, induces neuronal stress, cell death and causes functional deficits. Effectively blocking these effects of inflammation could, therefore, reduce both neuronal and functional decline. To test this hypothesis, we inhibited vascular adhesion protein 1 (VAP-1), a membrane-bound protein expressed on the endothelial cell surface, that mediates leukocyte extravasation and induces oxidative stress.MethodWe induced dopaminergic neuronal loss by infusing lipopolysaccharide (LPS) directly into the substantia nigra (SN) in rats and administered the VAP-1 inhibitor, PXS-4681A, daily.ResultsLPS produced: an acute inflammatory response, the loss of dopaminergic neurons in the SN, reduced the dopaminergic projection to SN target regions, particularly the dorsolateral striatum (DLS), and a deficit in habit learning, a key function of the DLS. In an attempt to protect SN neurons from this inflammatory response we found that VAP-1 inhibition not only reduced neutrophil infiltration in the SN and striatum, but also reduced the associated striatal microglia and astrocyte response. We found VAP-1 inhibition protected dopamine neurons in the SN, their projections to the striatum and promoted the functional recovery of habit learning. Thus, we reversed the loss of habitual actions, a function usually dependent on dopamine release in DLS and sensitive to striatal dysfunction.ConclusionsWe establish, therefore, that VAP-1 inhibition has an anti-inflammatory profile that may be beneficial in the treatment of dopamine neuron dysfunction caused by an acute inflammatory state in the brain.

Plasma PCSK9 levels increase following percutaneous coronary interventions

Abstract Background Beside its role in cholesterol homeostasis, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has been associated with the processes of vascular inflammation and atherosclerosis. The protein is expressed in endothelial cells, smooth muscle cells and macrophages and it is detected inside the human atherosclerotic plaque. Purpose We aimed to investigate the effect of acute inflammation associated with plaque rupture and vascular injury during elective percutaneous coronary intervention (PCI) on plasma levels of PCSK9 in patients with coronary artery disease (CAD). Methods We measured PCSK9, C-reactive protein (CRP), Interleukin-6 (IL-6) and high-sensitivity cardiac Troponin T (hs-cTnT) plasma levels immediately before and 18–24 hours after PCI via the radial approach, in 68 consecutive patients with stable CAD referred for elective PCI of a de novo lesion in a native coronary artery. Patients with unstable coronary syndrome &amp;lt;3 months old, baseline inflammatory condition, malignancy, auto-immune disease or intervention via the femoral access, were excluded. Results All patients were treated with balloon angioplasty and implantation of a second-generation drug eluting stent (DES). Baseline plasma levels of PCSK9 were higher in women and in patients treated with statins. At 18–24 hours after the procedure, plasma levels of PCSK9, CRP, IL-6 and hs-cTnT increased significantly compared to baseline (table). The change (elevation) in CRP plasma levels was statistically correlated with that of IL-6 (r=0.33; p=0.006) and with that of hs-cTnT (r=0.28; p=0.023). However, there was no correlation between the change (elevation) in plasma PCSK9 levels and those of IL-6 (r=−0.09; p=0.47), CRP (r=0.01; p=0.9), and hs-cTnT (r=0.1; p=0.41). Conclusions Plasma levels of PCSK9 increased by 26% following PCI with DES. That elevation was however, not correlated with the degree of myocardial injury (hs-cTnT) or of inflammation (IL-6 and CRP). The mechanism underlying PCK9 elevation post PCI requires further investigation. Funding Acknowledgement Type of funding sources: None.

ACTIVITY OF ANGIOTENSIN-CONVERSING ENZYME-2 IN ACUTE PULMONARY INFLAMMATION

Relevance. Angiotensin converting enzyme-2 (ACE2), which is the gateway to coronavirus, is also an important component of the tissue renin-angiotensin system with a number of anti-inflammatory effects. It is known that ACE2 is expressed in the lungs of patients with coronavirus pneumonia, but it is not clear how this depends on the stages of development and the severity of inflammation.&#x0D; Objective: to establish the effect of acute inflammation on pulmonary expression of angiotensin-converting enzyme-2.&#x0D; Material and methods. In Wistar rats (n=20), in compliance with bioethical standards, a sterile nylon thread 2.5 cm long and 0.2 mm thick to a depth of 2.5 cm was introduced into the trachea. The animals were observed and removed from the experiment at 7, 14, 21 and 28 days, microscopic and immunohistochemical (monoclonal antibodies against ACE2; clone 4G5.1; EMD Millipore Corporation; Temecula, CA US) studies were performed.&#x0D; Results. The microscopic picture of the lungs indicated the development of acute bronchopulmonary inflammation during the first week, the formation of peribronchial and alveolar abscesses in the second week with the onset of resolution of bronchopneumonia with the organization of abscesses in the third week and the development of diffuse fibrosis of the parenchyma and vascular hyalinosis in the fourth week of observation. The exudative phase of acute inflammation was accompanied by inhibition of ACE2 activity in bronchial epithelial cells, type II alveolocytes and vascular endothelium. With the transition of inflammation to the stage of proliferation and fibrosis, ACE2 activity was restored.&#x0D; Conclusion. The detected phase change in ACE2 activity can cause a wavy recurrent course of coronavirus infection, since an increase in the amount of ACE2 protein during attenuation of acute inflammation contributes to an increase in target cell infection.

Cecal Ligation and Puncture-Induced Sepsis Promotes Brown Adipose Tissue Inflammation Without Any Impact on Expression of Thermogenic-Related Genes.

Background and Aims: The negative effects of chronic low-level inflammation on adipose tissue physiology have been extensively demonstrated, whereas the effects of acute inflammation are less studied. Here, we aimed to investigate the effects of sepsis-induced acute inflammation on gene expression markers of brown and white adipose tissue functionality.Methods: Brown adipose tissue (BAT) and perirenal white adipose tissue (prWAT) gene expression markers were analyzed in cecal ligation and puncture (CLP)-induced sepsis mice model.Results: CLP-induced sepsis attenuated expression of adipogenesis-related genes, in parallel to increased Tnf, Il6, and Ltf gene expression in prWAT. In contrast, CLP-induced sepsis resulted in increased expression of pro-inflammatory genes (Il6, Ltf, and Lbp) in BAT, without affecting expression of genes encoding for thermogenic activity.Conclusion: Sepsis promotes both prWAT and BAT inflammation, associated with reduced adipogenesis-related gene expression in prWAT, without significant effects on BAT thermogenic genes.

Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study.

The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers’ age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116–13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity.

Efecto de la crioterapia en la articulación tibiotarsiana en el área de sección transversa del tibial anterior y el sóleo en ratas

Introducción. La crioterapia se usa para tratar la inflamación articular aguda, sin embargo su efecto sobre el músculo relacionado con la articulación inflamada aún no ha sido estudiado.Objetivo. Evaluar el efecto de la crioterapia sobre la articulación tibiotarsiana en el área de sección transversa (AST) de los músculos tibial anterior (TA) y sóleo en ratas con inflamación articular aguda.Materiales y métodos. Estudio experimental realizado en 32 ratas Wistar que fueron asignadas aleatoriamente a cuatro grupos: Control, Inflamación, Crioterapia-A y Crioterapia-B. El AST de las fibras de los músculos se midió 72 horas después de haberse iniciado el experimento.Resultados. En el tibial anterior hubo una reducción significativa del AST de las fibras musculares en los grupos Inflamación y Crioterapia-B en comparación con el grupo Control, mientras que en el grupo Crioterapia-A no se observó una reducción significativa en dicha área al compararlo con el Control. En el caso del músculo sóleo, se observó una reducción significativa del área en todos los grupos experimentales.Conclusión. El uso de crioterapia una vez al día por tres días atenúa el efecto atrófico de la inflamación articular aguda sobre el músculo TA, lo que confirma su importancia en el control del efecto deletéreo de la inflamación aguda sobre músculos de contracción rápida.

Paraoxonase 1, HDL Subclasses and Post Surgery Acute Inflammation: A Pilot Study.

High density lipoproteins (HDL) structure and function studies are needed to better understand the heterogeneous nature of the HDL particle, and its interaction with associated proteins such as apolipoprotein A-1 (ApoA-1), paraoxonase 1 (PON1) and the environment. Our study assesses the effects of acute inflammation on PON1 and HDL subclasses in post-surgical colorectal cancer patients. PON1 was measured kinetically through its arylesterase and lactonase activity and HDL sub-classes were measured using Quantimetrix Lipoprint® System. White blood cells (WBC) counts, c-reactive protein (CRP) and serum amyloid A (SAA) levels were also analyzed using standard techniques. Our findings show that baseline PON1 activity is lower in colorectal cancer patients and significant reductions are observed in the acute inflammatory state post-surgery. PON1 changes are also inversely related to inflammatory markers such as SAA and CRP. In addition, our preliminary findings show that small and intermediate HDL decreases post-op Day 1. In conclusion, our study demonstrates the effects of chronic and acute inflammation on PON1. Specifically, PON1 arylesterase and lactonase activity is lower in states of chronic inflammation and further decreased in the acute inflammatory state. Additionally, in our limited sample size, while changes in PON1 and HDL subclasses may be variable in the acute inflammatory period, small HDL decreased with a loss of PON1 activity in the subacute phase.

Influence of Fitness on Vascular Function in Young Adults during Acute Inflammation

Acute inflammation is associated with increased risk of cardiovascular events and impairs vascular function. Vascular function in this setting is most often interrogated by assessing endothelial function in conduit arteries, however, less is known regarding the downstream vascular tree including resistance artery and microvasculature function. Vascular dysfunction during acute inflammation may be attenuated by high cardiorespiratory fitness due to its association with improved vascular function and cardiovascular health.PURPOSEDetermine the effect of acute inflammation and fitness on conduit artery, resistance artery, and microvascular function.METHODSVascular function was assessed in 11 low fit (6 male, 24 ± 5 yrs, 22.8 ± 4.3 kg/m2, 34.5 ± 2.9 ml/kg/min) and 12 high fit (5 male, 27 ± 4 yrs, 22.6 ± 1.9 kg/m2, 56.4 ± 9.7 ml/kg/min) participants at baseline and 24h after a typhoid vaccination. Fitness was determined using a maximal treadmill test and those with a VO2peak &gt;75th age‐ and sex‐specific percentile according to the American College of Sports Medicine were considered high fit. Vascular assessments included flow‐mediated dilation (FMD) of the brachial artery via ultrasonography, forearm reactive hyperemia (RH) via venous occlusion plethysmography, and near‐infrared spectroscopy (NIRS) during a 5‐min arterial occlusion. Blood pressure was measured using an oscillometric cuff and C‐reactive protein (CRP) and interleukin‐6 (IL‐6) were assessed via standard ELISA techniques.RESULTSAcute inflammation was induced, as evident by increases in IL‐6 and CRP (p&lt;0.01, see Table). Mean arterial pressure did not change in either group (low fit: 92 ± 9 to 91 ± 8; high fit: 92 ± 10 to 91 ± 7). FMD was lower in the high fit group, yet both groups reduced FMD at 24h, even after controlling for shear rate (p&lt;0.05). No effect of acute inflammation was observed for forearm RH or NIRS (p&gt;0.05). High fit individuals, however, had greater microvascular reactivity with a quicker ability to accommodate increased blood flow (time to peak, group effect, p&lt;0.05).CONCLUSIONFitness did not alter the vascular response to acute inflammation, regardless of the level along the vascular tree. Both groups showed reductions in conduit artery endothelial function and no change in resistance artery or microcirculatory function, suggesting acute inflammation has non‐uniform effects on vascular function. Cardiorespiratory fitness did not influence the arterial response to inflammation, at least in this young, healthy population. Future studies need to evaluate the effects of acute inflammation in older individuals including those who are healthy and those with chronic health conditions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract A36: Characterizing the role of Egfr signaling in mediating the exacerbative effect of acute inflammation on tumor development in a mouse model for familial adenomatous polyposis

Abstract Over the past decade a number of inducible mouse models of intestinal tumor formation have been developed to study the genetic and cellular changes that contribute to colorectal cancer (CRC) development. Among them, the Lrig1-Cre/+;Apcfl/+ mice serve as a good model to study familial adenomatous polyposis (FAP), as the targeted elimination of one copy of the Apc gene in the Lrig1-expressing (Lrig1+) intestinal progenitor cells leads to loss of heterozygosity of the remaining wild-type Apc allele in the intestinal epithelium and eventually the formation of multiple histologically advanced adenomas in the distal colon. However, adenomas formed in the Lrig1-Cre/+;Apcfl/+ mice do not progress to adenocarcinomas. In order to develop a mouse model that recapitulates the process of CRC development in its entirety, we treated the Lrig1-Cre/+;Apcfl/+ mice with the proinflammatory reagent dextran sodium sulfate (DSS) and found that a single cycle of DSS right after tamoxifen-induced initial loss of one Apc allele significantly exacerbated tumor formation in the distal colon. Interestingly, DSS-treated Lrig1-Cre/+;Apcfl/+ mice also developed highly dysplastic tumors in the proximal colon, which is normally spared from tumor formation in the untreated Lrig1-Cre/+;Apcfl/+ mice. Using a newly developed chimeric Egfr protein reporter mouse, we are interrogating the roles of dysregulated epithelial and stromal Egfr signaling in promoting tumor development in the DSS-treated Lrig1-Cre/+;Apcfl/+;EgfrEmGFP/+ mice. Citation Format: Wei Li, Yu-Ping Yang, Robert J. Coffey, Jr. Characterizing the role of Egfr signaling in mediating the exacerbative effect of acute inflammation on tumor development in a mouse model for familial adenomatous polyposis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A36.

Acute intraperitoneal lipopolysaccharide influences the immune system in the absence of gut dysbiosis.

There is bidirectional communication between the immune system and the gut microbiome, however the precise mechanisms regulating this crosstalk are not well understood. Microbial‐associated molecular patterns (MAMPs) within the gut, including lipopolysaccharide (LPS) that produces a quick and robust activation of the immune system, may be one way by which these interactions occur. Endogenous levels of LPS in the gut are low enough that they do not usually cause disease, although, in times of increased LPS loads, they may be capable of increasing vulnerability of the gut to pathogenic bacteria. Furthermore, chronic, low‐grade inflammation can have lasting effects on the gut, but the effects of acute inflammation on gut communities have not been thoroughly assessed. In this study, we first investigated whether a single modest dose of LPS administered to adult male and female Siberian hamsters (Phodopus sungorus) activated the immune system by measuring levels of circulating cortisol and the proinflammatory cytokine TNF‐α in the liver compared with saline‐treated animals. We then investigated whether this same acute dose of LPS altered the microbiome 48 h after treatment. We found that, although LPS increased cortisol and liver cytokine levels, and produced changes in food intake and body mass in both sexes, immunological changes were independent of gut dysbiosis 48 h after LPS injection. These data suggest that an acute immune activation may not be capable of altering the gut microbiome in healthy individuals. It is likely, however, that this type of immune challenge may have other physiological impacts on the gut's vulnerability, and future studies will investigate these relationships further.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4–99.5%); specificity, 51.2% (35.1–67.1%); AUC, 0.688 (0.534–0.816)] and discharge modality [sensitivity, 87.5% (47.3–99.7%); specificity, 73.7% (56.9–86.6%), AUC, 0.789 (0.644–0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

A Ratiometric Near‐Infrared Fluorescent Probe for Quantification and Evaluation of Selenocysteine‐Protective Effects in Acute Inflammation

Selenocysteine (Sec) is a primary kind of reactive selenium species in cells whose antioxidant roles in a series of liver diseases have been featured. However, it is difficult to determine Sec in living cells and in vivo due to its high reactivity and instability. This work reports a ratiometric near‐infrared fluorescent probe (Cy‐SS) for qualitative and quantitative determination of Sec in living cells and in vivo. The probe is composed of heptamethine cyanine fluorophore, the response unit bis(2‐hydroxyethyl) disulfide, and the liver‐targeting moiety d‐galactose. Based on a detection mechanism of selenium–sulfur exchange reaction, the concentrations of Sec in HepG2, HL‐7702 cells, and primary mouse hepatocytes is determined as 3.08 ± 0.11 × 10−6m, 4.03 ± 0.16 × 10−6m and 4.34 ± 0.30 × 10−6m, respectively. The probe can selectively accumulate in liver. The ratio fluorescence signal of the probe can be employed to quantitatively analyze the fluctuation of Sec concentrations in cells and mice models of acute hepatitis. The experimental results demonstrate that Sec plays important antioxidant and anti‐inflammatory roles during inflammatory process. And the levels of intracellular Sec have a close relationship with the degree of liver inflammation. The above imaging detections make this new probe a potential candidate for the accurate diagnosis of inflammation.

Abstract P4-03-09: Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation

Abstract Previous research has demonstrated that chronic inflammation facilitates cancer progression and spread to other sites. The effect of acute inflammation in the microenvironment of the tumor that develops as a result of standard biopsy procedures has not been studied in detail. Recent studies demonstrated that acute inflammation in mouse models from a mammary biopsy increases the frequency of distal cancer metastasis. Core needle biopsies are the standard procedure for breast cancer diagnosis, but there have been no studies detailing the inflammatory response from the biopsy. The purpose of this study is to determine if core needle biopsies in breast cancer patients trigger an inflammatory response, determine the type of inflammatory response that occurs and study the potential effect of acute inflammatory response on tumor cells remaining. The biopsy wound site was identified in primary tumor resection samples from breast cancer patients. The inflammatory response adjacent and distant to the biopsy were studied via histology and immunohistochemistry. Tumor cell proliferation was studied as well. Our study demonstrated that diagnostic core needle biopsies trigger inflammatory cell recruitment at the site, and those cells remain over long periods of time. An unexpected increase in eosinophils were found to accumulate at the biopsy site. The biopsy also was shown to increase proliferation adjacent to the wound site. Overall, core needle biopsies used for breast cancer diagnosis induce a unique inflammatory environment at the site of the biopsy as well as the closely surrounding cells. Inflammation induced by the biopsy could lead to tumor cell progression or metastasis in breast cancer. These findings may be important for the clinical management of breast cancer. Citation Format: Spencer BL, Szalayova G, Ogodnik A, Rincon M, James T. Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-09.

Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation.

Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings may carry relevance in the clinical management of breast cancer.

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid-derived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid-initiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for invivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3-treated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel γ expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-κB by RvD3 and AT-RvD3 was seen invitro and by AT-RvD3 invivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injuredmucosa that accelerated restoration of epithelial barrier and function.