scholarly journals PSVII-3 Effects of oral administration of essential oils on anti-immune stress, antimicrobial and repairing the intestinal damage in broilers challenged by lipopolysaccharide

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 171-171
Author(s):  
Hanjin Oh ◽  
Shudong Liu ◽  
Won Yun ◽  
Jihwan Lee ◽  
Jiseon An ◽  
...  

Abstract The aim of the present study was to evaluate the effects of oral administration of essential oils (Carvacrol, Thyme and Oregano essential oils) on anti-immune stress, antimicrobial and repairing the intestinal damage, caused by Salmonella enterica Lipopolysaccharide, in vivo of broilers. A total of 100 ROSS 308 broilers (21-day-old; 1.10 ± 0.11kg) were randomly allocated to 5 groups, T1: basal diet + Saline; T2: basal diet + LPS; T3: basal diet+ 200μL carvacrol oils+ LPS; T4: basal diet+ 200μL thyme oils+ LPS; T5: basal diet+ 200μL oregano oils+ LPS, with 20 replicates every group, and 1 chicken per replicate per cage. The challenged by LPS resulted in an immune stress, which manifests as the abnormal growth (P < 0.05) in immune organs, the content of IgG (P < 0.05) and TNF-α(P < 0.05) and the rectum temperature (P < 0.05) increased compared with other groups; the oral administration of essential oils controlled the immune stress to a certain extent. The essential oils could withhold maleficent bacteria, as E. coli (P < 0.05) and Salmonella enumeration (P < 0.05), in vivo of the broiler. Meanwhile, the essential oils repaired the intestinal damage which shown a reduction in the villi height (P < 0.05) and goblet cell (P < 0.05) caused by LPS. In conclusion, the essential oils (Carvacrol, Thyme and Oregano essential oils) controlled the stress reaction and maintain intestinal health to a certain extent. http://www.conferenceharvester.com/

2019 ◽  
Vol 99 (2) ◽  
pp. 377-383
Author(s):  
S.D. Liu ◽  
M.H. Song ◽  
W. Yun ◽  
J.H. Lee ◽  
H.B. Kim ◽  
...  

The aim of the present study was to evaluate the effects of oral administration of essential oils (carvacrol, thyme, and oregano) on anti-immune stress, antimicrobial properties, and repairing the intestinal damage caused by Salmonella enterica lipopolysaccharides (LPS) in broilers. A total of 100 Ross 308 broilers (21-d-old; 1.10 ± 0.11 kg) were randomly allocated to five groups: T1, basal diet + saline; T2, basal diet + LPS; T3, basal diet + 200 μL carvacrol oils + LPS; T4, basal diet + 200 μL thyme oils + LPS; T5, basal diet + 200 μL oregano oils + LPS, with 20 replicates each, and one chicken per replicate per cage. Those challenged by LPS resulted in an immune stress, which manifests as the abnormal growth (P < 0.05) in immune organs, and the content of immunoglobulin G (P < 0.05), tumor necrosis factor-α (P < 0.05), and the rectum temperature (P < 0.05) increased compared with other groups. The oral administration of essential oils controlled the immune stress to a certain extent. The essential oils could reduce harmful bacteria, such as Escherichia coli (P < 0.05) and Salmonella enumeration (P < 0.05), in vivo of broilers. Meanwhile, the essential oils repaired the intestinal damage, which showed a reduction in the villi height (P < 0.05) and goblet cell (P < 0.05) caused by LPS. In conclusion, the essential oils (carvacrol, thyme, and oregano essential oils) controlled the stress reaction and maintained intestinal health to a certain extent.


2004 ◽  
Author(s):  
Πέτρος-Αχιλλέας Μαραγκουδάκης
Keyword(s):  
E Coli ◽  
Tnf Α ◽  

Σκοπός: Ο σκοπός της παρούσας διατριβής ήταν η εξέταση του προβιοτικού δυναμικού στελεχών οξυγαλακτικών βακτηρίων μέσω μίας σειράς in vitro δοκιμών, και της μετέπειτα εφαρμογής επιλεγμένων στελεχών σε in vivo μοντέλα ποντικών έναντι της λοίμωξης του Η. pylori και της ελκώδους κολίτιδας, αλλά και σε τεχνολογικό επίπεδο στην παρασκευή γιαουρτιού.Υλικά και μέθοδοι: Στη διατριβή αυτή μελετήθηκαν 51 στελέχη Lactobacillus του Εργαστηρίου Γαλακτοκομίας του Γεωπονικού Πανεπιστημίου Αθηνών, απομονωμένα κυρίως από γαλακτοκομικά προϊόντα και κόπρανα προβάτων, καθώς και 22 στελέχη Enterococcus και Streptococcus, απομονωμένα από κόπρανα προβάτων. Τα στελέχη αυτά εξετάστηκαν σε μία σειρά in vitro δοκιμών που αφορούν την επιβίωσή τους σε συνθήκες εξομοίωσης του ανθρώπινου γαστρεντερικού συστήματος, οι οποίες περιελάμβαναν επιβίωση σε χαμηλό pH, επιβίωση παρουσία των πρωτεολυτικών ενζύμων πεψίνη και παγκρεατίνη, και επιβίωση παρουσία χολικών αλάτων.Στην συνέχεια τα στελέχη εξετάστηκαν σε δοκιμές βασικές για την ασφάλεια χρήσης τους στον ανθρώπινο οργανισμό. "Ολα τα στελέχη δοκιμάστηκαν ως προς την αιμολυτική τους δραστικότητα, και τα στελέχη γαλακτοβακίλλων συγκεκριμένα για την ανθεκτικότητά τους έναντι επιλεγμένων αντιβιοτικών.Παράλληλα, εξετάστηκαν in vitro βασικές ιδιότητες που θεωρούνται επιθυμητές για τα προβιοτικά στελέχη, όπως υδρόλυση των χολικών αλάτων, μελέτη της υδροφοβίας και της ικανότητας πρόσδεσης των γαλακτοβακίλλων σε κύτταρα Caco-2, ικανότητά διέγερσης κυττάρων του ανθρώπινου οργανισμού (PBMCs), καθώς και μελέτη της αντιμικροβιακής δράσης έναντι παθογόνων βακτηρίων και της δυνατότητάς αναστολής της πρόσδεσης παθογόνων σε κύτταρα Caco-2.Στην συνέχεια πραγματοποιήθηκαν in vivo μελέτες σε ποντίκια, για την εξακρίβωση του προβιοτικού χαρακτήρα επιλεγμένων στελεχών. Τα στελέχη L. casei Shirota ACA-DC 6002 και L. paracasei subsp. tolerans ACA-DC 4037 χορηγήθηκαν σε ποντίκια επιμολυσμένα με Η. pylori και αξιολογήθηκε η επίδραση των γαλακτοβακίλλων αυτών στον αποικισμό του παθογόνου και στην αξιολόγηση του βαθμού και της δραστικότητας στο στομάχι. Επίσης, τα στελέχη αυτά χρησιμοποιήθηκαν και για την πρόληψη TNBS- κολίτιδας σε ποντίκια.Τέλος, επιλεγμένα στελέχη γαλακτοβακίλλων αξιολογήθηκαν για την τεχνολογική τους εφαρμογή, μελετώντας την ικανότητά οξίνϊσης του γάλακτος και τη χρήση τους ως καλλιέργειες για την παρασκευή γιαούρτηςΑποτελέσματα: Ορισμένα στελέχη βρέθηκαν να έχουν ικανοποιητική επιβίωση σε συνθήκες εξομοίωσης του ανθρώπινου πεπτικού συστήματος. Κανένα στέλεχος δεν βρέθηκε να έχει ισχυρή (β-) αιμολυτική δράση, ενώ η αντοχή των γαλακτοβακίλλων έναντι επιλεγμένων αντιβιοτικών δεν παρουσιάστηκε διαφορετική από την έμφυτη και αναμενόμενη, ανάλογα το είδος των εξεταζόμενων γαλακτοβακίλλων, ενώ αρκετά στελέχη παρουσίασαν ικανότητα υδρόλυσης χολικών αλάτων. Τα στελέχη παρουσίασαν ποικιλόμορφη πρόσδεση στους οργανικούς διαλύτες, αλλά γενικά τα περισσότερα στελέχη δεν παρουσίασαν μεγάλη υδροφοβία, ενώ αρκετά στελέχη γαλακτοβακίλλων παρουσίασαν ικανοποιητική πρόσδεση σε κύτταρα Caco-2 (>5%), με το στέλεχος L. plantarum ACA-DC 146 (25% πρόσδεση) να ξεχωρίζει. Το ίδιο στέλεχος, μαζί με το L. paracasei subsp. tolerans ACA-DC 4037 βρέθηκαν να προκαλούν την έκκριση υψηλών επιπέδων φλεγμονωδών κυτταροκινών (IL-12, TNF-α και IFN-γ) από PBMCs, ενώ αντίθετα το στέλεχος L. casei Shirota ACA-DC 6002 προκάλεσε την έκκριση της αντιφλεγμονώδους κυτταροκίνης IL-10. Παρόλο που κανένα από τα υπερκείμενα των στελεχών δεν παρεμπόδισε τα στελέχη E. coli, S. typhimurium και Η. pylori, ορισμένα στελέχη, όπως τα L. casei Shirota, L. plantarum ACA-DC 146 και L. paracasei subsp. tolerans ACA-DC 4037 προκάλεσαν την αναστολή της πρόσδεσης εντερικών παθογόνων (E. coli και S. typhimurium) σε κύτταρα Caco-2 σε επίπεδα μέχρι και 50%.In vivo, η χορήγηση του L. casei Shirota ACA-DC 6002 σε ποντίκια οδήγησε στην μείωση του βαθμού και της δραστικότητας της γαστρίτιδας αλλά και στον αποικισμό του Η. pylori. Παρόμοια αποτελέσματα, αλλά σε μικρότερη έκταση, παρατηρήθηκαν με την χορήγηση του στελέχους L. paracasei subsp. tolerans ACA-DC 4037. Παράλληλα, το στέλεχος L. casei Shirota ACA-DC 6002 δείχνει να παρέχει προστασία σε ποντίκια κατά την πρόκληση ελκώδους κολίτιδας με την χορήγηση TNBS.Σε τεχνολογικό επίπεδο, κανένα από τα εξεταζόμενα στελέχη δεν παρουσίασε υψηλή ικανότητα οξύνισης στο γάλα και κατά συνέπεια δεν ήταν δυνατόν να χρησιμοποιηθούν ως εναρκτήριες καλλιέργειες για την παρασκευή γιαούρτης. Από την άλλη, καθώς κανένα στέλεχος δεν παρεμποδίζει αλλά και δεν παρεμποδίζεται από τις παραδοσιακές εναρκτήριες καλλιέργειες γιαούρτης, ήταν δυνατή η χρήση τους ως συμπληρωματικές καλλιέργειας για την παρασκευή γιαούρτης. Στην συνέχεια επιλεγμένα στελέχη χρησιμοποιήθηκαν για το σκοπό αυτό και το στέλεχος L. paracasei subsp. tolerans ACA- DC 4037 ξεχώρισε όταν χρησιμοποιήθηκε ως συμπληρωματική καλλιέργεια για την παρασκευή γιαούρτης με εμβόλιο πηγμένου γάλακτος (1% ν/ν) στους 42°C, λόγω της υψηλής μικροβιακής, φυσικοχημικής και οργανοληπτικής ποιότητας του προϊόντος. Συμπεράσματα: Τα στελέχη L. casei Shirota ACA-DC 6002, L. plantarum ACA-DC 146 και L. paracasei subsp. tolerans ACA-DC 4037, επέδειξαν υποσχόμενο προβιοτικό δυναμικό κατά την διάρκεια εκτεταμένων in vitro και in vivo δοκιμών. Η μελέτη αυτή επιβεβαιώνει τις προβιοτικές ιδιότητες του L. casei Shirota και επιδεικνύει την πιθανή εφαρμογής του στη λοίμωξη του Η. pylori και στην ελκώδη κολίτιδα στον άνθρωπο. Επιπλέον, το στέλεχος L paracasei subsp. tolerans ACA-DC 4037 διαθέτει επίσης δυναμικό χρήσης έναντι του Η. pylori αλλά και στην παρασκευή ενός επιτυχημένου προβιοτικού γιαουρτιού. Τέλος, το στέλεχος L. plantarum ACA-DC 146 μπορεί να εξεταστεί in vivo σε μοντέλα αλλεργικών αντιδράσεων, λόγω της υψηλής αντιφλεγμονώδους επίδρασής τους σε ανθρώπινα περιφερειακά μονοπύρηνα (PBMCs.)


2013 ◽  
Vol 3 (1) ◽  
pp. 6 ◽  
Author(s):  
Ted H. Elsasser ◽  
Stanislaw Kahl ◽  
Katie M. Lebold ◽  
Maret G. Traber ◽  
Jessica Shaffer ◽  
...  

While vitamin E has been used for decades in cattle diets, the principle form used traditionally is the synthetic α-isoform acetate or succinate and largely no data exist on the biological partitioning or functionality of the major naturally occurring γ- and δ-isoforms in cattle. Using tyrosine 3’-nitrated protein (pNT) as a biomarker of nitrosative cell stress, we sought to evaluate the effectiveness of short-term feeding supplementation of high content natural α-tocopherol (<em>α-T</em>, 96% α-isomer) compared to high content γ- and δ-enriched low α-content mixed tocopherol oils (<em>γ-T</em>, ~70% <em>γ-</em>, 20% δ-, &lt;5% α-isoform) to mitigate systemic and hepatic aspects of the proinflammatory response to endotoxin (LPS). Calves fed diets supplemented with <em>α-T</em>, <em>γ-T</em> for five days or no tocopherol supplement (<em>T0E</em>) were challenged with a low-level of LPS (0.25 μg/kg, iv, <em>E. coli </em>055:B5) sufficient to effect a liver nitration response. As fed,<em> α-T</em> or <em>γ-T</em> increased plasma and liver content of the respective tocopherols reflecting their relative abundance in the respective diets. Plasma or tissue mediators and biomarkers of the proinflammatory response [plasma concentrations of tumor necrosis factor-α (TNF-α, P&lt;0.001), nitrate+nitrite (NOx, P&lt;0.01), and serum amyloid A (SAA, P&lt;0.001)], and general liver content of pNT (P&lt;0.005) increased after LPS. LPS-mediated increases in TNF-α were not dif- ferent between diet treatments; both plasma NOx (P&lt;0.05) and generalized liver pNT (P&lt;0.03) responses were attenuated significantly in <em>α-T </em>and <em>γ-T versus T0E calves</em>. Plasma SAA was significantly decreased in γ-T calves at 24 h post-LPS relative to responses in <em>α-T</em> or <em>T0E </em>calves. The nitration of the mitochondrial proteins 24 h post-LPS was not only attenuated in <em>α-T</em> and <em>γ-T vs T0E</em>, but also the mitigating effect of <em>γ-T</em> on these specific nitration events was greater than that of <em>α-T </em>(P&lt;0.01). Results are consistent with the concept that short-term <em>α-T</em> or <em>γ-T</em> supplementation can effectively decrease proinflammatory liver pNT after LPS; some mitochondrial nitration targets may be better protected with prophylactic supplementation with γ-,δ-tocopherol enriched oil.


1992 ◽  
Vol 1 (5) ◽  
pp. 347-353 ◽  
Author(s):  
Andrew C. Issekutz ◽  
Nancy Lopes ◽  
Thomas B. Issekutz

The cytokines IL-1 and TNF-α are involved in inflammation and their production is stimulated by various agents, especially endotoxin (LPS). Here, using the human IL-1 receptor antagonist (IL-1RA) and a new monoclonal antibody (mAb 7F11) to rabbit TNF, the role of endogenous IL-l and TNF production in acute (3h) leukocyte (PMNL) recruitment to dermal inflammation in rabbits has been studied. IL-1RA inhibited by 27% the PMNL accumulation in reactions induced by killed Escherichia coli (p < 0.05) but not by LPS. The monoclonal antibody to TNF inhibited by 27% and 38% (p < 0.002) the PMNL accumulation in LPS and E. coli reactions respectively, but a combination of the mAb with IL-1RA was not more effective. Treatment of human umbilical vein endothelium with LPS for 3 h activated endothelium to induce PMNL transendothelial migration in vitro, which was not inhibited by IL-1RA, antibody to TNF-α, IL-1 or to IL-8. In conclusion, TNF and IL-1 may partially mediate acute PMNL infiltration in vivo to LPS and Gram negative bacteria, but there is a major IL-1/TNF independent mechanism, at least in dermal inflammation, which may be due to direct LPS activation of the microvasculature or perhaps the generation of cytokines other than IL-1 and TNF.


2022 ◽  
Vol 8 ◽  
Author(s):  
Kaibin Mo ◽  
Jing Li ◽  
Fenfen Liu ◽  
Ying Xu ◽  
Xianhui Huang ◽  
...  

Essential oils (EOs) have long been considered an alternative to antibiotics in the breeding industry. However, they are unstable and often present unpleasant odors, which hampers their application. Microencapsulation can protect the active gradients from oxidation and allow them to diffuse slowly in the gastrointestinal tract. The purpose of this study was to investigate the effect of microencapsulation technology on the biological function of EOs and the possibility of using microencapsulate EOs (MEEOs) as an alternative to antibiotics in weaning piglets. First, we prepared MEEOs and common EOs both containing 2% thymol, 5% carvacrol and 3% cinnamaldehyde (w/w/w). Then, a total of 48 weaning piglets were randomly allotted to six dietary treatments: (1) basal diet; (2) 75 mg/kg chlortetracycline; (3) 100 mg/kg common EOs; (4) 500 mg/kg common EOs; (5) 100 mg/kg MEEOs; and (6) 500 mg/kg MEEO. The trial lasted 28 days. The results showed that piglets in the 100 mg/kg MEEOs group had the lowest diarrhea index during days 15–28 (P &lt; 0.05). In addition, 100 mg/kg MEEOs significantly alleviated intestinal oxidative stress and inflammation (P &lt; 0.05), whereas 500 mg/kg common EOs caused intestinal oxidative stress (P &lt; 0.05) and may lead to intestinal damage through activation of inflammatory cytokine response. MEEOs (100 mg/kg) significantly reduced the ratio of the relative abundance of potential pathogenic and beneficial bacteria in the cecum and colon (P &lt; 0.05), thus contributing to the maintenance of intestinal health. On the other hand, chlortetracycline caused an increase in the ratio of the relative abundance of potential pathogenic and beneficial bacteria in the colon (P &lt; 0.05), which could potentially have adverse effects on the intestine. The addition of a high dose of MEEOs may have adverse effects on the intestine and may lead to diarrhea by increasing the level of colonic acetic acid (P &lt; 0.05). Collectively, the results suggest that microencapsulation technology significantly promotes the positive effect of EOs on the intestinal health of weaning piglets and reduces the adverse effect of EOs, and 100 mg/kg MEEOs are recommended as a health promoter in piglets during the weaning period.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Tenghao Wang ◽  
Jie Fu ◽  
Xiao Xiao ◽  
Zeqing Lu ◽  
Fengqin Wang ◽  
...  

A novel bacteriocin secreted by Clostridium butyricum ZJU-F1 was isolated using ammonium sulfate fractionation, cation exchange chromatography, affinity chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC). The bacteriocin, named CBP22, contained 22 amino acids with the sequence PSAWQITKCAGSIAWALGSGIF. Analysis of its structure and physicochemical properties indicated that CBP22 had a molecular weight of 2264.63 Da and a +1 net charge. CBP22 showed activity against E. col K88, E. coli ATCC25922, and S. aureus ATCC26923. The effects and potential mechanisms of bacteriocin CBP22 on the innate immune response were investigated with a lipopolysaccharide- (LPS-) induced mouse model. The results showed that pretreatment with CBP22 prevented LPS-induced impairment in epithelial tissues and significantly reduced serum levels of IgG, IgA, IgM, TNF-α, and sIgA. Moreover, CBP22 treatment increased the expression of the zonula occludens and reduced permeability as well as apoptosis in the jejunum in LPS-treated mice. In summary, CBP22 inhibits the intestinal injury and prevents the gut barrier dysfunction induced by LPS, suggesting the potential use of CBP22 for treating intestinal damage.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Okawa ◽  
A Yamawaki-Ogata ◽  
Y Narita ◽  
H Munakata ◽  
R Hashizume ◽  
...  

Abstract Objective The pathogenesis of aortic aneurysm (AA) is characterized by the chronic inflammation of the aortic wall with the accumulation of macrophages and the degradation of the extracellular matrix (ECM) including elastin. Colchicine (COL) is an alkaloid derived from the plant Lily family Colchicum autumnale, and it is known for anti-inflammatory effects. Plant extracts containing COL have been used in the treatment of gout from ancient period. Currently, pseudogout, familial Mediterranean fever, Behçet's disease and pericarditis are also treated by COL. Furthermore, recent evidence suggests the use of COL for secondary prevention of cardiovascular disease, and the phase 3 clinical trial for it has begun. The objective of this study is to investigate whether COL could prevent the progression of aortic aneurysms. Methods In vitro: Macrophages (J774A.1 cell line) stimulated TNF-α 24 hours before and smooth muscle cell (SMC) were cultured with 10 ng/mL COL, and the gene expression of inflammatory cytokines involved in the AA formation was measured 24 hours later. In vivo: Male apolipoprotein E-deficient mice (30–35 weeks of age) were infused with angiotensin II for 28 days. COL (20 μg/kg/d) or saline (NS, as a control) was administered orally to the mice every day (COL group, n=8; NS group, n=8). Aortic diameter was measured by echography every week and all mice were sacrificed and their thoracoabdominal aorta was harvested at the last day of the administration period and elastin content, MMP activitis, and levels of inflammatory cytokines involved in the AA formation were measured. Results In vitro: The gene expression of IL-1β, TNF-α, MCP-1, NF-κB, MMP-9 in the macrophages was significantly decreased in the COL group. The gene expression of Lox, TIMP-2 in the SMC were significantly increased in COL group. In vivo: Aortic diameter measured by echography every week was significantly suppressed in the COL group (2.25 vs 2.81 mm, p<0.05). The incidence of AA was decreased in the COL group (62.5% vs 100%). COL significantly suppressed the degeneration of aortic elastin in EVG staining (p<0.05). There is no significant difference in the enzyme activities of MMP-2 and MMP-9 between COL and NS groups, but IL-1β (54.4 vs 81.4, p<0.05), TNF-α (31.0 vs 60.6, p<0.05), MCP-1 (258.2 vs 411.2, p<0.05), NLRP3 inflammasome (7.1 vs 8.6, p<0.05), NE (1.5 vs 2.4, p<0.05), MPO (44.9 vs 48.1, p<0.05) were decreased in the COL group. Discussion In AA model mice, COL seems to suppress the progression of AA by anti-infammation and preservation of the ECM structure through the inhibition of NLRP3 inflammasome. That NLRP3 inflammasome activation leads to the progression of AA in AA model mice was previously reported and this supports out results. Methods and Results (in vivo) Conclusions This results suggest that the oral administration of COL prevents the progression of AA in AA model mice and it is expected as a novel therapeutic agent for AA. Acknowledgement/Funding JSPS KAKENHI Grant


2000 ◽  
Vol 68 (8) ◽  
pp. 4422-4429 ◽  
Author(s):  
Wei Cui ◽  
David C. Morrison ◽  
Richard Silverstein

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.


Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4300-4307 ◽  
Author(s):  
Yoko Nakano ◽  
Shigehiko Imagawa ◽  
Ken Matsumoto ◽  
Christian Stockmann ◽  
Naoshi Obara ◽  
...  

Abstract Erythropoietin (Epo) gene expression is under the control of hypoxia-inducible factor 1 (HIF-1), and is negatively regulated by GATA. Interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), which increase the binding activity of GATA and inhibit Epo promoter activity, are increased in patients with anemia of chronic disease (ACD). We previously demonstrated the ability of K-7174 (a GATA-specific inhibitor), when injected intraperitoneally, to improve Epo production that had been inhibited by IL-1β or TNF-α treatment. In the present study, we examined the ability of both K-11706, which inhibits GATA and enhances HIF-1 binding activity, and K-13144, which has no effect on GATA or HIF-1 binding activity, to improve Epo production following inhibition by IL-1β or TNF-α in Hep3B cells in vitro and in an in vivo mouse assay. Oral administration of K-11706 reversed the decreases in hemoglobin and serum Epo concentrations, reticulocyte counts, and numbers of erythroid colony-forming units (CFU-Es) induced by IL-1β or TNF-α. These results raise the possibility of using orally administered K-11706 for treating patients with ACD.


2007 ◽  
Vol 35 (02) ◽  
pp. 317-328 ◽  
Author(s):  
Jun Liu ◽  
Zheng-Tao Wang ◽  
Li-Li Ji

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism. Oral administration of neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of neoandrographolide (100–150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Respiratory bursts were quantified by chemiluminescence (CL) measurements.Results showed that neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 μM to 150 μM. Neoandrographolide also inhibited NO and TNF-α production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata. These results indicate that neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.


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