Inflammation In Guinea Pigs Research Articles

Berberine Improves Histopathological Changes of Allergic Airway Inflammation in Guinea Pigs

<p><strong>Background and Objective:</strong> Berberine has anti-inflammatory properties through pathways that are also involved in asthma. Therefore, it is postulated that it will be effective in reducing airway inflammation in the allergic asthmatic model. The objective of the current study was to observe the effects of berberine on the histopathology of lungs in sensitized Guinea pigs and compare the changes with that of the standard drug, dexamethasone.</p>
 <p><strong>Methods:</strong> This experimental study was conducted at the Postgraduate Medical Institute, Lahore, Pakistan, from February 2016 to April 2016. Twenty-four healthy Guinea pigs were divided randomly into four groups: normal control, Ovalbumin (OVA ) group, OVA + berberine group, and OVA + dexa group. The last three groups were sensitized on days 0 and 14 and challenged on days 25, 26, and 27 with OVA. Berberine and dexamethasone were administered intraperitoneally to the respective groups before each challenge. The animals were then sacrificed on day 28 under anesthesia, lungs were dissected, and tissue samples were assessed microscopically for morphology and status of inflammation in each group. Data were analyzed by applying the Kruskal-Wallis analysis of variance test followed by the Mann Whitney U test using SPSS 20.</p>
 <p><strong>Results:</strong> The comparison of histopathological changes revealed that the infiltration of inflammatory cells in the lung airways was significantly higher (p-value ≤0.01) in the OVA group as compared to the normal control group. Both OVA + berberine and OVA + dexa groups showed a reduction in total lung inflammation (p-value ≤0.01 vs. OVA group) equally. The effect of berberine on epithelial changes was nonsignificant (p-value 0.206 vs. OVA group), while dexamethasone showed significant improvement as compared to the OVA group (p-value 0.007). However, the difference between berberine and dexamethasone treatment was nonsignificant (p-value ≤0.05).</p>
 <p><strong>Conclusion: </strong>It was concluded that berberine improved the histopathological score of lung inflammation in sensitized Guinea pigs, equivalent to that of dexamethasone, with lesser effects on epithelial changes.</p>

Endocannabinoid metabolism inhibition ameliorates ovalbumin-induced allergic airway inflammation and hyperreactivity in Guinea pigs

AimsEndocannabinoids are biologically active cannabinoid-related substances endogenously synthesized in many mammalian tissues. Mainly two enzymes carry out their degradation; Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL). Endocannabinoids are shown to affect the modulation of inflammatory processes and airway responsiveness. In the present study, we investigated the effects of FAAH and MAGL inhibitor treatments in experimental allergic airway inflammation in guinea pigs. Materials and methodsGuinea pigs were sensitized and challenged by ovalbumin to induce an allergic asthma model. Then, the effects of FAAH inhibitor URB597, MAGL inhibitor JZL184, and dual (FAAH/MAGL) inhibitor JZL195 on airway inflammation and hyperreactivity were evaluated. Key findingsOvalbumin challenge increased airway reactivity, IgE in serum, IL-4, and IL-13, and the percentage of eosinophils in bronchoalveolar lavage (BAL). In addition, inhibition of FAAH or MAGL enzymes leads to an increase in endocannabinoid levels. The selective inhibition of the FAAH enzyme prevented inflammation indicators such as cytokine production and inflammatory cell infiltration but had a negligible effect on airway hyperreactivity. However, the inhibition of the MAGL enzyme or dual inhibition of both FAAH and MAGL enzymes tent to moderate both pulmonary inflammation and airway hyperreactivity. SignificanceWe have previously demonstrated that modulation of endocannabinoid levels in the airways by FAAH or MAGL inhibition can be useful in preventing acute lung inflammation. The results of the present study further suggest that FAAH and MAGL inhibitor treatment can also be a promising strategy for bronchial hyperreactivity and airway inflammation in allergic asthma.

Evaluation of anti-inflammatory effect of omega 3 polyunsaturated fatty acid in Guinea pigs

: We need drugs to decrease inflammation as well as have very less side effects. Review of literature mentioned anti-inflammatory action of Omega 3 fatty acids. Hence, we selected this drug. Our aim was to find the anti-inflammatory effect of Omega 3 fatty acid using animal model.: The study is objective animal study where measurement of inflammation was done by observational methodology, for the present study four groups were made- 6 Guinea pigs in each group. Control guinea pigs were fed distilled water, second group standard drug indomethacin 4mg/ kg body wt, test group 1 received 1200mg/kg body wt, test group II received 2400mg/kg body wt of Omega 3 fatty acid. All drugs given orally 30 minutes before exposure to UV radiation of 30 seconds duration was given and inflammation was observed at 6, 12 and 24 hrs after UV exposure in the form of scoring.Statistical significance was calculated using Anova method. For statistical analysis we have used SPSS system version 20. Inflammation was observed in all the four groups of Guinea pigs, there was significant anti-inflammatory effect of omega 3 fatty acid in the dose of 1200mg/kg body wt and 2400mg/kg body wt at 12 and 24 hours. Omega 3 fatty acids 1200mg/kg body wt orally produced significant anti-inflammatory effect against UV radiation induced inflammation in Guinea pigs at 12 and 24 hrs. However, standard drug could produce significant anti-inflammatory effect only at 24 hrs in comparison to control group. The anti-inflammatory effects of test 1, test 2 groups and standard group are comparable.

The anti-asthmatic potential of flavonol kaempferol in an experimental model of allergic airway inflammation

Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-β1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-β1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).

Determination of Phosphodiesterase Inhibitors Tadalafil, Roflumilast and Roflumilast N-Oxide Using LC-MS in Guinea Pig Plasma.

Phosphodiesterases are known as a super-family of 11 isoenzymes, which can exert various functions based on their organ distribution. In this work, a rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed for quantification of tadalafil (phosphodiesterase five inhibitor), roflumilast (RF) (phosphodiesterase four inhibitor) and its active metabolite, RF N-oxide in guinea pig plasma. Chromatographic separation was carried out on UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) at a flow rate 0.5 mL/min, using 0.2% formic acid in acetonitrile and 0.2% formic acid in water as mobile phases within 4 min. Detection was performed using a triple quadrupole mass spectrometer employing electrospray ionization operated in positive mode using multiple reaction monitoring mode. The method utilized deuterium labeled internal standards, and was validated according to European Medicines Agency guidelines. It showed excellent linearity in the range of 0.5-500.0 ng/mL for all analytes with coefficient of determination >0.99. The intra- and inter-day precisions (relative standard deviation %) were within 6.7%, and the recoveries were greater than 73.4%. Using this method, plasma samples from experiments of phosphodiesterase four, and five inhibitors in a model of ovalbumin-induced allergic inflammation in guinea pigs were analyzed.

Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism.

To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver.

Stigmasterol Modulates Allergic Airway Inflammation in Guinea Pig Model of Ovalbumin-Induced Asthma.

We explored the potential benefits of stigmasterol in the treatment of asthma, an airway disorder characterized by immune pathophysiology and with an ever-increasing worldwide prevalence. We assessed the modulatory effect of the intraperitoneal administration of stigmasterol on experimentally induced airway inflammation in guinea pigs. The effect of stigmasterol on inflammatory cell proliferation, oxidative stress, lung histopathology, and remodeling was investigated. The results showed significant suppressive effects on ovalbumin-induced airway inflammatory damage. Stigmasterol at 10–100 mg/kg reduced proliferation of eosinophils, lymphocytes, and monocytes while reducing peribronchiolar, perivascular, and alveolar infiltration of inflammatory cells. Histopathology revealed stigmasterol maintained lung architecture and reversed collagen deposition, an index of lung remodeling. Overexpression of serum vascular cell adhesion molecule-1 (VCAM-1) and ovalbumin-specific immunoglobulin E (OVA sIgE) elicited by ovalbumin sensitization and challenge was significantly controlled with stigmasterol. Taken together, stigmasterol possessed significant antiasthmatic properties and had suppressive effects on key features of allergen-induced asthma.

Role of selective blocking of bradykinin receptor subtypes in attenuating allergic airway inflammation in guinea pigs

The present study was designed to evaluate the potential role of bradykinin antagonists (R-715; bradykinin B1 receptor antagonist and icatibant; bradykinin B2 receptor antagonist) in treatment of allergic airway inflammation in comparison to dexamethasone and montelukast. R-715 as dexamethasone significantly decreased peribronchial leukocyte infiltration, bronchoalveolar lavage fluid (BALF) albumin and interleukin 1β as well as serum OVA-specific IgE level. Also, R-715 like montelukast significantly decreased BALF cell count (total and eosinophils). Icatibant showed negative results. The current findings suggest that selective bradykinin B1 receptor antagonists may have the therapeutic potential for the treatment of allergic airway inflammation.

Centenary of the death of Elie Metchnikoff: a visionary and an outstanding team leader

Elie Metchnikoff passed away on July 15th, 1916. He is considered to be the father of phagocytes, cellular innate immunity, probiotics, and gerontology. In all of these fields, he was a visionary. To achieve such a notability and produce so many masterpieces, Metchnikoff used more than 30 animal species to support his findings, and his pasteurian laboratory published more than 200 papers in the Annales de l’Institut Pasteur. As a wonderful team leader and a great mentor, during his 28 years at Institut Pasteur, he welcomed and supervised more than 100 young trainees. Trained as an embryologist, he contributed to the birth of immunology and to the understanding of physiology and pathology. Indeed, Metchnikoff and his team investigated inflammation in guinea pigs, rats, frogs; studied infectious diseases in monkeys, caimans, geese; investigated aging in parrots, dogs, humans; proposed hypotheses to understand age-associated senility using rabbits and humans; developed germ free tadpoles, flies, chicks; studied the gut flora in bats, horses, birds, humans; and popularized the use of probiotics as a tool to delay the deleterious effects of toxic compounds derived from putrefactive gut bacteria. He was also a philosopher and penned essays on human disharmony and on pessimism and optimism.

Y-27632 is associated with corticosteroid-potentiated control of pulmonary remodeling and inflammation in guinea pigs with chronic allergic inflammation.

BackgroundPreviously, we showed that treatment with the Rho-kinase inhibitor Y-27632 was able to control airway responsiveness, inflammation, remodeling, and oxidative stress in an animal model of asthma, suggesting that this drug is beneficial in asthma. However, studies evaluating the effects of these inhibitors in conjunction with corticosteroids on chronic pulmonary inflammation have not been conducted. Therefore, we evaluated the effects of treatment with the Rho-kinase inhibitor Y-27632, with or without concurrent dexamethasone treatment, on airway and lung tissue mechanical responses, inflammation, extracellular matrix remodeling, and oxidative stress in guinea pigs with chronic allergic inflammation.MethodsThe guinea pigs were subjected to seven ovalbumin or saline inhalation exposures. Treatment with Y-27632 (1 mM) and dexamethasone (2 mg/kg) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the pulmonary mechanics were evaluated and exhaled nitric oxide (ENO) levels were determined. The lungs were removed and histological analysis was performed using morphometry.ResultsThe treatment of guinea pigs with the Rho-kinase inhibitor and dexamethasone (ORC group) decreased ENO, the maximal mechanical responses after antigen challenge, inflammation, extracellular matrix remodeling and oxidative stress in the lungs.This therapeutic strategy reduced the levels of collagen and IFN-γ in the airway walls, as well as IL-2, IFN-γ, 8-iso-PGF2α and NF-κB in the distal parenchyma, when compared to isolated treatment with corticosteroid or Rho-kinase inhibitor (P < 0.05) and reduced the number of TIMP-1-positive cells and eosinophils in the alveolar septa compared to corticosteroid-treated animals (P < 0.05). The combined treatment with the Rho-kinase inhibitor and the corticosteroid provided maximal control over the remodeling response and inflammation in the airways and parenchyma.ConclusionsRho-kinase inhibition, alone or in combination with corticosteroids, can be considered a future pharmacological tool for the control of asthma.

Immune complex disease in guinea pig lungs: elicitation with pigeon serum.

Immune complex- and T cell-mediated reactions to organic antigens appear to contribute to the pathogenesis of hypersensitivity pneumonitis in humans. Because pigeon serum is one of the reagents used by clinicians to diagnose this disease, we assessed its potential to elicit immune complex-mediated pulmonary inflammation in guinea pigs. Animals were immunized with different concentrations of pigeon serum protein emulsified in complete Freund's adjuvant, and serums were collected at 4-day intervals after the booster injection. The largest amounts of tissue-fixing (IgG1) and complement-fixing (IgG2) antibodies to pigeon serum were detected in guinea pigs immunized with 1.0 mg of pigeon serum protein 20 to 24 days after the secondary immunization. Therefore, the responses of these animals and of recipients of serum from these animals to aerosol challenge with either homologous (pigeon serum) or heterologous (bovine gamma globulin) immunogen was investigated. Actively and passively immunized guinea pigs developed pulmonary inflammation only after exposure to aerosolized pigeon serum. However, lesions were not observed in the lungs of complement-deficient recipients of immune serum that had inhaled homologous immunogen. These observations suggest that such pigeon serum-elicited pulmonary inflammation in guinea pigs is a manifestation of a complement-dependent, humoral-immune mechanism of pathogenesis and thus is consistent with an immune complex disease.

The effect of selective antagonist of H4 receptor JNJ7777120 on nasal symptoms, cough, airway reactivity and inflammation in guinea pigs

The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n=8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5mg/kg i.p. 30min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p<0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.

A Lutein Nano‐Emulsion is more Effective than Regular Lutein in Protecting Cholesterol‐Induced Liver Injury by Increasing Lutein Bioavailability in Guinea Pigs

Regular lutein (R‐lutein) vs lutein prepared in nano‐emulsion (NANO) (average particle diameter = 250 nm) were compared on their effects in reducing hepatic steatosis and liver inflammation in guinea pigs with diet‐induced liver injury. Twenty four guinea pigs were divided into 3 groups (8/group) and were fed for 6 weeks either a hypercholesterolemic diet (0.25g/100g dietary cholesterol) only (control) or in combination with 3 mg/d of R‐Lutein or 3 mg/d of lutein as NANO. Plasma lutein was 3 times higher in the NANO group compared to the R‐Lutein group (68.3 vs 22.7 nmol/L, respectively) while there was no detectable plasma lutein in control guinea pigs. Lutein concentrations in liver (p&lt; 0.001), adipose (p&lt; 0.001) and eyes (p&lt; 0.001) were greater in the NANO, intermediate in the R‐Lutein and almost non‐existent in the control group indicating that lutein in NANO is more easily absorbed and delivered to the target tissues. Further, guinea pigs fed NANO lutein had hepatic steatosis scores of 2.04 ± 0.53 which were lower than those found in control (2.50 ± 0.45) or in guinea pigs from the R‐lutein group (2.63± 0.26) (p&lt; 0.025). Inflammatory cytokines, Interleukin (IL)‐1 beta and Monocyte chemoattractant protein‐1 were lower in the NANO group compared to the R‐Lutein or the control groups (p&lt;0.05). These results indicate that utilizing a nano‐delivery mechanism, results in higher lutein bioavailability and a greater protection against hepatic steatosis and inflammation

A nano‐emulsion of lutein is more effective than regular lutein in reducing hepatic inflammation in guinea pigs (1044.15)

The purpose of this study was to compare the effects of consuming regular lutein versus lutein in a nano‐emulsion on hepatic liver enzymes and gene expression inflammatory markers in guinea pigs. For that purpose, we fed guinea pigs a hypercholesterolemic (0.25 g/100g dietary cholesterol) diet for 12 weeks to induce liver injury. Guinea pigs consumed either 0.9 mg/d of regular lutein (control) (n= 8 guinea pigs) or a nano‐emulsion (NANO) (average diameter 422 nm) (n = 8 guinea pigs). Plasma lipids and glucose were not different between treatments. However hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST), markers of liver function were 54 and 50% lower, respectively in guinea pigs fed the NANO emulsion (p&lt; 0.005). Hepatic and plasma lutein were measured by HPLC and gene expression was evaluated by use of RT‐PCR. There were no significant differences between groups in either plasma or hepatic lutein concentrations, although there was a trend for higher plasma lutein in the NANO group (p=0.084). Gene expression of monocyte chemoattractant protein‐1 was not different between groups. In contrast although the expression of tumor necrosis factor (TNF)‐alpha was 70% higher in guinea pigs fed the control group, they were not different between groups due to the high variability. These results indicate that using the same amount of dietary lutein, a nano‐emulsion is more effective in protecting the liver against diet‐induced inflammation.Grant Funding Source: UConn Experimental Station

Inhibitory effect of sihuangxiechai decoction on ovalbumin-induced airway inflammation in Guinea pigs.

The aim of this study was to investigate the effect of sihuangxiechai decoction on asthmatic Guinea pig model which was sensitized by intraperitoneal (i.p.) injection of ovalbumin (OVA) and challenged by OVA inhalation to induce chronic airway inflammation. Differential cell counts of cytospins were performed after staining with Giemsa solution. The quantity of leukocytes and its classification in bronchoalveolar lavage fluid (BALF) and blood were evaluated by blood cell analyzer and microscope. Histological analysis of the lung was performed by hematoxylin and eosin (H&E) staining. The levels of interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in BALF and serum were detected by radioimmunoassay (RIA). The total number of leukocytes in BALF and blood has no significant difference between Sihuangxiechaitang decoction treated group and dexamethasone (DXM) treated group but was significantly lower than those of asthma group. The percentage of eosinophils in lung tissues of sihuangxiechai decoction treated group was significantly lower than that of asthma group. The results demonstrated that the levels of IL-4 and TNF-α in the sihuangxiechai decoction treated group were significantly reduced compared with the asthma group. In conclusion, these findings demonstrate that sihuangxiechai decoction has a protective effect on OVA-induced asthma in reducing airway inflammation and airway hyperresponsiveness (AHR) in a Guinea pig model and may be useful as an adjuvant therapy for the treatment of bronchial asthma.

Influence of roflumilast on airway reactivity and apoptosis in ovalbumin-sensitized Guinea pigs.

Chronic inflammatory diseases, associated with airway obstruction and cough, are usually treated with bronchodilating and anti-inflammatory drugs. Inhibition of phosphodiesterases (PDE) leads to both of these effects and influences apoptosis of immune cells. In chronic obstructive pulmonary disease, roflumilast, a selective PDE4 inhibitor, has been recently approved for pharmacotherapy. The aim of this study was to evaluate the effect of long-term administration of roflumilast in experimental allergic inflammation in guinea pigs. Male adult guinea pigs were used in the study. There were four experimental groups sensitized with ovalbumin for 14days and thereafter treated per os, by inhalation, and intraperitoneally for 7days with roflumilast or vehicle. A control group was left without sensitization. Roflumilast reduced specific airway resistance after nebulization of histamine, as measured in a double-chamber whole-body plethysmograph. This effect was confirmed in in vitro organ bath, with significant decreases in tracheal and lung smooth muscle contractility after cumulative doses of histamine. Suppression of hematological and immunological markers of inflammation and enhanced apoptosis in animals treated with roflumilast points to the possibility of a beneficial effect of roflumilast in allergic inflammation.

Influence of Oral Tolerance on Lung Cytokines Expression and Oxidative Stress Activation in Guinea Pigs with Chronic Inflammation

Objective: We had previously demonstrated that oral induced tolerance attenuates lung tissue hyperresponsiveness, eosinophil inflammation and extracellular matrix remodelling in a model of chronic inflammation in guinea pigs. In the present study, we evaluated if these responses were associated to alterations on Th1/Th2 cell expression on airways and distal lung. Methods: Animals received seven inhalations of ovalbumin (1-5 mg/mL; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). After the last inhalation, lungs were removed for the histological analysis using morphometry. We assessed IL-2, IL-4, IL-13, IFN-γ and iNOS both in airways and distal lung. Results: There was an increase in IL-2, IL-4, IL-13, IFN-γ and iNOS positive cells both in airways and alveolar septa in ovalbumin-exposed guinea pigs compared with controls (P<0.05). Both in airways and in lung tissue there was a decrease in IL-4, IL-13 and iNOS positive cells in OT1 and OT2 compared to OVA (P<0.05). Considering IL-2 expression, there was an increase in OT1 and OT2 compared to OVA (P<0.05). We observed positive correlations among the functional responses and some inflammation and oxidative stress pathway activation markers evaluated, especially in alveolar wall. Conclusion: Oral tolerance induces a shift in Th1/Th2 and influences oxidative stress activation both in airways and distal lung of animals with chronic pulmonary allergic inflammation. These results may clarify the mechanisms involved in the attenuation of mechanical responsiveness, inflammation and remodelling of airways and distal lung by oral tolerance, as previously shown in this animal model.

Therapeutic potential of anti-IL-1β IgY in guinea pigs with allergic asthma induced by ovalbumin

BackgroundInterleukin-1 beta (IL-1β) plays pivotal roles in the progression of allergic airway inflammation. This study aims to determine whether the blockade of IL-1β can inhibit airway inflammation in guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin (OVA). MethodsHealthy guinea pigs treated with saline were used as normal controls (group C). The guinea pigs with allergic asthma induced by the inhalation of aerosolized OVA were randomly divided into three groups: (1) the M group containing negative control animals treated with saline; (2) the Z1 group containing animals treated by the inhalation of atomized 0.1% anti-IL-1β immunoglobulin yolk (IgY); and (3) the Z2 group containing positive control animals that were treated with budesonide. The inflammatory cells in the peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were evaluated using methylene blue and eosin staining. Cytokine concentrations were measured using an enzyme-linked immunosorbent assay. Pulmonary sections were examined using hematoxylin-eosin staining. ResultsAllergic inflammation and damage to the pulmonary tissues were decreased in the Z1 group compared to the M group. Eosinophils and neutrophils in the PB and BALF were significantly decreased in the Z1 group compared to the M group (P<0.05). Treatment with anti-IL-1β IgY significantly reduced the levels of IL-1β, IL-4, IL-8, IL-13, TNF-α, TGF-β1 and IgE in the BALF (P<0.05). ConclusionThe inhalation of aerosolized anti-IL-1β IgY inhibits pathological responses in the pulmonary tissues of guinea pigs with allergic asthma. The inhibitory activity may be due to the decrease in the numbers of eosinophils and neutrophils and the reduced levels of inflammatory cytokines and IgE in the PB and BALF.

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8mg/kg), moguisteine (24mg/kg), LVDP (14mg/kg) and naringin (18.4mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

Toll-like Receptor 7 Rapidly Relaxes Human Airways

Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs. To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs. To evaluate the relaxant effects of other TLRs. Human airway smooth muscle strips were contracted with methacholine in vitro, and responses to TLR7 and TLR8 agonists were assessed. TLR7-mediated nitric oxide production was measured using a fluorescent indicator, and TLR7 expression was characterized using immunofluorescence. TLR7 signaling was also evaluated in ovalbumin-challenged guinea pigs. The TLR7 agonist imiquimod (R837) caused rapid dose-dependent relaxation of methacholine-contracted human airways in vitro. This was blocked by the TLR7 antagonist IRS661 and by inhibiting nitric oxide production but not by inhibiting prostaglandin production. TLR7 activation markedly increased fluorescence of a nitric oxide detector. TLR7 was expressed on airway nerves, but not airway smooth muscle, implicating airway nerves as the source of TLR7-induced nitric oxide production. TLR7-mediated relaxation persisted in inflamed guinea pigs airways in vivo. The TLR8 agonists polyuridylic acid and polyadenylic acid also relaxed human airways, and this was not blocked by the TLR7 antagonist or by blocking nitric oxide or prostaglandin production. No other TLRs relaxed the airways. TLR7 is expressed on airway nerves and mediates relaxation of human and animal airways through nitric oxide production. TLR7-mediated bronchodilation may be a new therapeutic strategy in asthma.