Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic consequences induced by experimental food allergy.

The prevalence of food allergy is rising in the western world. Allergen restriction is the chosen treatment in this condition, but continuous ingestion of the antigen has shown positive results in clinical trials. In a previous study, we have shown several allergic and metabolic alterations after 7 days of ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to investigate whether prolonged ingestion of antigen by sensitized mice would reverse the metabolic consequences caused by experimental food allergy. For this, allergic and metabolic parameters were analysed after prolonged ingestion of an OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA consumption, sensitized mice showed increased serum levels of anti-OVA immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and adipose tissue weight loss, followed by adipose tissue inflammation and decreased serum levels of adipokines, glucose and triglycerides. However, after 14 days of oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice that were only sensitized, but the specific IgG1 did not change. With this prolonged ingestion of OVA, sensitized mice were protected from OVA-induced anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal. Moreover, various parameters analysed were significantly ameliorated, including adipose tissue inflammation, body and adipose tissue loss, as well as serum levels of adipokines and triglycerides. Therefore, our data suggest that prolonged ingestion of OVA by sensitized mice results in an improvement of the metabolic consequences caused by experimental food allergy.

Effect of Saccharomyces cerevisiae UFMG A-905 in a murine model of food allergy.

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.

Chronic antigen ingestion protects ovalbumin sensitized mice from severe manifestation of Leishmania major infection.

In the present work, the development of experimental leishmaniasis was examined in sensitized BALB/c mice that were chronically fed with antigen. After an oral challenge with egg white solution, the ovalbumin (Ova)-sensitized mice showed an increase in serum anti-Ova IgE and IgG1 antibodies. Lesions induced by Leishmania major infection were reduced by the ingestion of Ova in sensitized mice, as assessed by reduced footpad growth, lower parasite loads and improved pathological outcome compared to sham sensitized mice. Moreover, such findings were connected to a shift to a Th1 response involving higher IFN-gamma production and serum levels of IgG2a anti-Leishmania antigens. The data appear to corroborate the suggestion that chronic ingestion of an antigen by sensitized mice modulates the immunological system through a shift in cytokine release, exhibiting a healing response and resistance to L. major infection.

The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation.

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING-/- mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING-/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

Gelatin intake increases the atheroma formation in apoE knock out mice.

The effect of gelatin ingestion on cholesterol metabolism and on atheroma formation was evaluated in both wild type (n=14) and apoprotein E (apoE) knock out (apoE(-/-)) (n=20) C57BL/6 7-week-old mice. Animals were fed a cholesterol-free isoproteic semi-purified diet containing 20% of casein (control diet) or 10% of casein plus 10% of gelatin (gel diet) for 8 weeks. In wild type mice, dietary gelatin caused a reduction in the serum triacylglycerols levels associated with an increase in the fecal excretion. No difference in blood cholesterol was seen at the sixth week of experiment. At the eighth week of experiment, there was a modest but significant reduction of serum total and high density lipoprotein (HDL) cholesterol in apoE(-/-) mice fed on gel diet compared to the control. Total cholesterol/HDL cholesterol ratio was 2-fold higher in the gel group than that seen in the control group (14.39 and 7.84, respectively). Histological analyzes showed a 2.2-fold increase in the dimension of the atherosclerotic plaques in the proximal aorta in apoE(-/-) mice fed on a gel diet compared to those fed on a control diet. The gel diet also promoted a reduction in the fecal excretion of bile acids. Hepatic cholesterol was similar in both groups. In conclusion, although gelatin reduced total serum cholesterol, this reduction was associated to a decrease of HDL cholesterol and consequent increase of total cholesterol/HDL cholesterol ratio, resulting in an acceleration of atherogenesis.

Effects of the PAF receptor antagonist UK74505 on local and remote reperfusion injuries following ischaemia of the superior mesenteric artery in the rat.

The effects of the long lasting and potent PAF receptor antagonist UK74505 were assessed on the local and remote injuries following ischaemia and reperfusion (I/R) of the superior mesenteric artery (SMA) in rats. In a severe model of ischaemia (120 min) and reperfusion (120) injury, in addition to the local and remote increases in vascular permeability and neutrophil accumulation, there was significant tissue haemorrhage, blood neutropenia, systemic hypotension and elevated local and systemic TNF-alpha levels. Post-ischaemic treatment with the selectin blocker fucoidin (10 mg kg(-1)) prevented neutrophil accumulation in tissue and, in consequence, all the local and systemic injuries following severe I/R. Treatment with an optimal dose of UK74505 (1 mg kg(-1)) also reversed local and remote neutrophil accumulation, increases in vascular permeability and intestinal haemorrhage. UK74505 partially inhibited blood neutropenia and reperfusion-induced hypotension. Interestingly, both fucoidin and UK74505 prevented the local, but not systemic, increases of TNF-alpha levels following severe I/R injury, demonstrating an important role of migrating cells for the local production of TNF-alpha. However, the results do not support a role for PAF as an intermediate molecule in the production of systemic TNF-alpha. The beneficial effects of UK74505 and other PAF receptor antagonists in models of I/R injury in animals and the safety of UK74505 use in man warrant further investigations of the use of this drug as preventive measure for I/R injury in humans.

Mechanisms underlying eosinophil trafficking and their relevance in vivo.

After their formation in the bone marrow, eosinophils circulate with a short half-life and are distributed throughout the body, especially in mucosal and sub-mucosal regions. Although a small amount of these cells are normally seen in healthy tissue, blood and tissue eosinophilia is a hallmark of helminthic and allergic diseases. The role of eosinophils in the normal physiology of mucosal tissues is not understood, but there is good evidence to demonstrate that these cells protect the host at least against some intestinal helminths, specially those with a lung cycle. In addition, there are now many data that support a role for eosinophils in the pathophysiology of allergic diseases, such as asthma. Because helminthic diseases have been largely controlled in developed countries, there has been much interest in the development of drugs which affect eosinophil migration and/or activation in the tissue and which may, thus, be useful in the treatment of allergic conditions. The understanding of the mechanisms controlling eosinophil trafficking and/or activation are essential in the development of anti-eosinophil-based therapeutic strategies. The present paper reviews aspects of eosinophil biology with emphasis on the role of eosinophils in parasitic infections and allergy, the basic mechanisms underlying the trafficking of eosinophils into tissue and how these can be modulated pharmacologically.

A method of decontaminating Strongyloides venezuelensis larvae for the study of strongyloidiasis in germ-free and conventional mice.

To study the possible influence of intestinal micro-organisms on the course of strongyloidiasis in mice, a method was developed to obtain axenic infective larvae of Strongyloides venezuelensis. Cultured larvae from conventional mice were treated with sodium hypochlorite 0.25% for 10 min, washed in distilled water and then exposed to various combinations of antibiotics for 30 or 60 min. Success was achieved with a combination of penicillin 180 mg/L and ceftazidime 1 mg/ml. Decontamination of the larvae was determined by aerobic and anaerobic culture and by inoculation into gnotobiotic mice. Viability was established by subcutaneous inoculation of larvae into germ-free and conventional mice. Preliminary results showed that gnotobiotic mice were more susceptible than conventional mice to infection with axenic S. venezuelensis larvae as judged by faecal egg excretion, recovery of worms in the small intestine and histopathological examination of the duodenal mucosa. These results suggest that the normal intestinal flora protects the host against experimental infection with S. venezuelensis.

Effects of a BLT receptor antagonist on local and remote reperfusion injuries after transient ischemia of the superior mesenteric artery in rats.

Reperfusion of ischemic vascular beds may lead to recruitment and activation of leukocytes, release of mediators of the inflammatory process and further injury to the affected vascular bed and to remote sites. Neutrophils appear to play a major role in the pathophysiology of reperfusion injury. Amongst inflammatory mediators shown to activate neutrophils and induce their recruitment in vivo, much interest has been placed on the role of leukotriene (LT)B(4). Here, we have assessed the effects of the BLT receptor antagonist (+)-1-(3S, 4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid (CP 105,696) in a model of neutrophil-dependent ischemia and reperfusion injury in the rat. The superior mesenteric artery was isolated and ischemia was induced by its total occlusion for 30 min. After 30 min of reperfusion, injury was assessed by evaluating the extravasation of Evans blue, an index of vascular permeability, and the levels of myeloperoxidase, an index of neutrophil accumulation, in the intestine, mesentery and lung. The neutrophil-dependence of the local (intestine and mesentery) and remote (lung) injury was confirmed by using fucoidin, a selectin blocker, and WT-3, an anti-CD18 monoclonal antibody. Post-ischemic treatment with CP 105,696 dose-dependently inhibited vascular permeability and neutrophil accumulation in the intestine and mesentery. CP 105,696 also blocked the vascular permeability changes, but not neutrophil accumulation, in the lungs after reperfusion injury. Virtually identical results were obtained with another BLT receptor antagonist, 1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)-heptoxy++ +)-phenyl )ethanone (LY255283). Our results suggest that post-ischemic treatment with BLT receptor antagonists may inhibit local and remote ischemia and reperfusion injury by blocking both the accumulation and/or activation of neutrophils.

Evaluation of the components of a commercial probiotic in gnotobiotic mice experimentally challenged with Salmonella enterica subsp. enterica ser. Typhimurium.

Vitacanis((R)), a probiotic preparation containing a Lactobacillus acidophilus, an Enterococcus faecium and a Saccharomyces cerevisiae, has been developed for the prevention of intestinal disorders in dogs and cats. In the present study, these microorganisms were tested jointly or singly during experimental infection of gnotobiotic mice with Salmonella Typhimurium. Four experimental groups consisting of animals given probiotics jointly or singly and a control group consisting of germfree mice were used. The groups were treated with one or three of the microorganisms (experimental) or PBS (control) 10 days before intragastric challenge with a suspension containing about 10(2) cells of the bacterial pathogen. A higher survival (P<0.05) was observed in gnotobiotic mice given E. faecium (82%). All the animals in the other groups died after the challenge but the survival time was longer (P<0.05) for groups given all three of the microorganisms (7.4+/-2.4 days) or given only L. acidophilus (7.2+/-2.9 days) than for the control mice (4.4+/-1.1 days) and the mice that received S. cerevisiae (4.9+/-1.6 days) mice. The survival data agreed with the histopathological findings which showed more severe liver and intestinal lesions in control mice and in mice given Saccharomyces. In vitro antagonistic assays showed inhibition growth of E. faecium and S. Typhimurium around the colonies of L. acidophilus and for S. Typhimurium around the colonies of E. faecium. However, in vivo, S. Typhimurium became similarly established in the digestive tract of gnotobiotic mice at levels ranging from 10(8) to 10(10)CFU/g of feces and remained at these high levels until the animals died or were sacrificed. Among the three probiotic components of the commercial product Vitacanis((R)), E. faecium was the only one that provided protection against challenge with S. Typhimurium. Protection was not due to the reduction of the intestinal populations of the pathogenic bacteria.

Effect of hyperosmotic sodium chloride solution on vascular permeability and inflammatory edema in rats.

This study analyzes the effects of treatment with a hyperosmotic NaCl solution on carrageenan-induced inflammatory edema and vascular permeability in rats. Given 15 min before carrageenan, this treatment reduced paw edema measured for up to 6 h by 27 to 44%. Similarly, when the rats were treated 30 min after injection of the irritant, paw volume was significantly reduced (35 to 53%) between 1 and 6 h when compared to that of untreated animals. Increases in vascular permeability were significantly reduced at 30 min (73%) and 1 h (54%) in rats treated 15 min before, and at 1 h (49%) in animals treated 30 min after carrageenan. Treatment with hyperosmotic mannitol or isotonic NaCl solutions did not show any changes in inflammatory response to carrageenan. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.

Effect of i.v. administered hyperosmotic sodium chloride on carrageenan-induced pleurisy in adrenalectomized and intact rats.

The effect of administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on carrageenan-induced pleurisy was determined in adrenalectomized and intact rats. The volume of the pleural exudate was significantly reduced 4 h after induction by treatment with hyperosmotic NaCl for both adrenalectomized (0.08 +/- 0.16 ml) and intact (0.03 +/- 0.08 ml) animals compared to their untreated controls (0.56 +/- 0.44 ml and 0.26 +/- 0.15 ml, respectively). Similarly, hyperosmotic NaCl treatment significantly reduced the total number of inflammatory cells in the pleural cavity: 29.60 x 10(6) +/- 7.80 x 10(6) cells for adrenalectomized animals and 28.90 x 10(6) +/- 11.43 x 10(6) cells for intact animals compared to 63.67 x 10(6) +/- 19.92 x 10(6) and 45.26 x 10(6) +/- 12.71 x 10(6) cells for their untreated controls. Treatment with isotonic saline did not affect carrageenan-induced pleurisy. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.

Immunological induction of flavor aversion in mice.

1. Young adult BALB/c and B6D2F1 mice of both sexes (20 +/- 2 g) immunized ip with 2 doses of 10 micrograms ovalbumin (Ova), but not with 2 doses of 10 micrograms bovine gammaglobulins (BGG), show aversion to the ingestion of sweetened egg white or crystallized Ova solutions which are avidly ingested by normal mice. In 24 h, normal mice or mice immunized with BGG ingested, respectively, 340 +/- 80 and 265 +/- 56 mg of sweetened egg white per gram of body weight (mg/gbw); in the same period, Ova-immunized mice ingested less than one tenth these amounts (18 +/- 5 mg/gbw). ELISA-titers of anti-Ova and anti-BGG antibodies in immune mice were of similar magnitude. 2. Aversion arises coincidentally with the emergence of anti-ovalbumin antibodies in serum in the primary response, 14 days after primary immunization. 3. Previous induction of oral tolerance to ovalbumin by a single gavage with 20 mg Ova 7 days before primary ip immunization, which blocks the increase of specific antibodies in serum, also blocks the development of the aversive phenomenon. 4. Aversion was induced to 1 mg/ml but not 0.1 mg/ml sweetened crystallized ovalbumin solutions and was already noticeable 2 h after exposure of immunized mice to sweetened egg white solutions. 5. We conclude that, at least in experimental situations, immunological factors may be of decisive importance in diet selection.

Hepatic changes in mice chronically infected with Helicobacter trogontum.

We infected NIH germ-free female mice with Helicobacter trogontum, a recently described intestinal bacterium of rats, in order to study the lesions it induced in the liver of this host. Fifteen mice were challenged with a single dose of H. trogontum (test group) and killed 6, 12 and 18 months after inoculation (5 animals/group). Nine animals were challenged with 0.85% saline alone (control group) and killed at the same times. Fragments from the liver, cecum and colon were obtained for microbiologic and histologic examination. Stool samples were also collected. H. trogontum was detected in the cecum, colon and/or stool samples of all test mice. As expected, the bacterium was not isolated from any specimen obtained from the control animals. On the other hand, although we could not cultivate the bacterium from the liver, 13 test animals (86.7%) presented histological changes in this organ. The 6-month group presented infiltration of mononuclear and polymorphonuclear cells in the hepatic parenchyma and the two other groups presented foci of mononuclear cells. The results suggest that H. trogontum can elicit a hepatic inflammatory response in mice since the only difference between control and test animals was the presence of H. trogontum in the latter. This result, together with the growing number of related reports in the literature, reinforces the possible role of Helicobacter infection in the pathogenesis of hepatobiliary diseases.

Immunization by subcutaneous implants of polyester-polyurethane sponges coupled with antigen.

A new protocol is described for immunization of outbred Swiss mice. The procedure is based on subcutaneous implantation of antigen-coupled polyester-polyurethane sponges cut into disks of 10 mm in diameter vs 2 mm in thickness. Antigen coupling was performed by overnight incubation of the sponge with a solution of ovalbumin (Ova) (2 mg/ml) diluted in sodium carbonate buffer, pH 9.6. The amount of ovalbumin that was taken up by the sponge was between 71.4 to 82.5 micrograms. This was estimated by comparing the Ova absorbance at 280 nm in coating buffer solutions before and after incubation. To compare the efficiency of the proposed method, experimental groups immunized with the antigen in the presence of adjuvants (10 micrograms in Al(OH)3 or 100 micrograms in complete Freund's adjuvant (CFA)) were run in parallel. The data obtained after the 3rd week of immunization indicate that both cellular and humoral immune responses were achieved. These were assayed by antigen-induced footpad swelling and ELISA (specific antibodies), respectively. The levels of both immune responses elicited were similar to the responses observed in mice immunized with ovalbumin in the presence of Al(OH)3. The method might represent an advantage when immunizing with pathogenic antigens. Preliminary experiments have suggested that the antigen remains immobilized or bound to the sponge for a long period of time, since there is an increment on the cell population inside the sponges after boosting the animals. If so, the undesirable effects of immunization would be reduced.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice.

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20% loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100%) and increased mucus production (483%). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice.

Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 10(8) cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.

Influences of alpha-tocopherol on cholesterol metabolism and fatty streak development in apolipoprotein E-deficient mice fed an atherogenic diet.

Although the role of oxidized lipoproteins is well known in atherogenesis, the role of vitamin E supplementation is still controversial. There is also little information about cholesterol metabolism (hepatic concentration and fecal excretion) in the new models of atherosclerosis. In the present study, we evaluated the effect of moderate vitamin E supplementation on cholesterol metabolism and atherogenesis in apolipoprotein E (apo E)-deficient mice. Apo E-deficient mice were fed an atherogenic diet containing 40 or 400 mg/kg of alpha-tocopherol acetate for 6 weeks. Total cholesterol in serum and liver and 3-OH-alpha-sterols in feces, and fecal excretion of bile acids were determined and histological analyses of aortic lesion were performed. A vitamin E-rich diet did not affect body weight, food intake or serum cholesterol. Serum and hepatic concentrations of cholesterol as well as sterol concentration in feces were similar in both groups. However, when compared to controls, the alpha-tocopherol-treated mice showed a reduction of about 60% in the atherosclerotic lesions when both the sum of lesion areas and the average of the largest lesion area were considered. These results demonstrate that supplementation of moderate doses of alpha-tocopherol was able to slow atherogenesis in apo E-deficient mice and to reduce atherogenic lipoproteins without modifying the hepatic pool or fecal excretion of cholesterol and bile acids.

Reciprocal interference of experimental dyslipidemia and food allergy in the evolution of both diseases.

Background. Food allergies have been shown to reduce serum triacylglycerol, glucose, cholesterol, and free fatty acid levels in mice. In turn, dyslipidemias, especially dyslipidemias presenting with low levels of HDL cholesterol, are important risk factors for the development of atherosclerosis. However, the consequences of food allergies on dyslipidemia and atherosclerosis have not been fully investigated. Methods. Food allergy was induced using an egg white solution (EWS) in ovalbumin- (OVA-) sensitized C57BL/6 and low-density lipoprotein receptor knockout mice (LDLr(-/-)) for 5 weeks and was confirmed by the high production of anti-OVA IgE and IgG1 antibodies in both mouse strains. Results. The allergic C57BL/6 mice exhibited EWS aversion that was associated with less visceral fat and high levels of anti-Ova IgE antibodies after 5 weeks of EWS intake compared to controls. However, LDLr(-/-) allergic mice showed reduced anti-Ova IgE levels that were similar to the nonsensitized group. The LDLr(-/-) allergic mice also demonstrated a reversal of food aversion and sustained visceral fat after 5 weeks of allergy. Although HDL cholesterol levels were reduced in both sensitized mouse strains, lipid deposition in thoracic and abdominal aorta as well as area and composition of atherosclerotic plaques as unaffected by chronic ingestion of EWS. Conclusion. LDLr(-/-) mice develop an attenuated food allergy, as they showed a reversal of food aversion and lower IgE production after 5 weeks of induced allergy. The development of atherosclerosis, in turn, was not accelerated in the allergic LDLr(-/-) group despite the more atherogenic lipid profile.

AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma.

BACKGROUND AND PURPOSE: AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1-7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation. EXPERIMENTAL APPROACH: We used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 µg·mouse(-1) , i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg(-1) ·per day, s.c.) or saline (100 µL·kg(-1) ·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates. KEY RESULTS: Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs. CONCLUSIONS AND IMPLICATIONS: AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1-7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.