Carbon monoxide attenuates aeroallergen-induced inflammation in mice

Carbon monoxide (CO) generated by catalysis of heme by heme oxygenase is increased in the exhaled air of asthmatic patients. Based on recent studies demonstrating that asthma is an inflammatory disease associated with increased oxidants and that CO confers cytoprotection in oxidant-induced lung injury and inflammation, we sought to better understand the functional role of CO in asthma by using an aeroallergen model. Mice were sensitized to ovalbumin, challenged with aerosolized ovalbumin, and maintained in either CO (250 parts/million) or room air for 48 h. The differential effects of CO on bronchoalveolar lavage (BAL) fluid cell types were observed, with a marked attenuation of BAL fluid eosinophils in the CO-treated animals at 24 and 48 h. A marked reduction of the proinflammatory cytokine interleukin-5 was observed in the CO-treated mice, with no significant changes for other proinflammatory cytokines. These differential effects of CO were also observed with leukotrienes (LTs) and prostaglandins in that CO significantly decreased BAL fluid PGE2, and LTB4 but exerted negligible effect on thromboxane B2 or LTC4/D4/E4. Our data suggest a putative immunoregulatory role for CO in aeroallergen-induced inflammation in mice.     

Inhaled budesonide inhibits OVA-induced airway narrowing, inflammation, and cys-LT synthesis in BN rats.

The objective of the present investigation was to examine the effects of an inhaled glucocorticoid, budesonide, on antigen-induced production of cysteinyl leukotrienes (cys-LTs) and pulmonary inflammatory cell infiltration in the Brown Norway rat, an animal model of asthma. Two weeks after sensitization to ovalbumin, rats were treated with budesonide (2.5 mg/kg) 18 and 1 h before challenge with antigen. Budesonide abolished the late response to ovalbumin (P<0.02) and strongly inhibited the in vivo synthesis of N-acetyl-leukotriene E(4), an indicator of cys-LT synthesis, during this period (P<0.005). Both total bronchoalveolar lavage (BAL) cells (P<0.01) and BAL macrophages (P<0.005) were markedly reduced to approximately 25% of their control levels after treatment with budesonide. It can be concluded that inhibition of the antigen-induced late response in Brown Norway rats by budesonide is associated with reductions in both BAL macrophages and cys-LT synthesis. It is possible that the effect of budesonide on cys-LT synthesis is related to its effects on pulmonary macrophages.     

Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.     

Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma

Chronic airway inflammation is a key feature of bronchial asthma. Leukotrienes are potent inflammatory mediators that play a role in the pathophysiology of asthma, and their levels are elevated in the airways in response to allergen challenge. We examined the anti-inflammatory effect of thymoquinone (TQ), the active principle in the volatile oil of Nigella sativa seeds, on leukotriene (LT) biosynthesis in a mouse model of allergic asthma. Mice sensitized and challenged with ovalbumin (OVA) antigen had an increased amounts of leukotriene B4 and C4, Th2 cytokines, and eosinophils in bronchoalveolar lavage (BAL) fluid. In addition, there was also a marked increase in lung tissue eosinophilia and goblet cell numbers. Administration of TQ before OVA challenge inhibited 5-lipoxygenase, the main enzyme in leukotriene biosynthesis, expression by lung cells and significantly reduced the levels of LTB4 and LTC4. This was accompanied by a marked decrease in Th2 cytokines and BAL fluid and lung tissue eosinophilia, all of which are characteristics of airway inflammation. These results demonstrate the anti-inflammatory effect of TQ in experimental asthma.     

Identification with MRI of the pleura as a major site of the acute inflammatory effects induced by ovalbumin and endotoxin challenge in the airways of the rat

Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and na?ve, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites.     

Alteration of alveolar macrophage chemotaxis,cell adhesion,and cell adhesion molecules following ozone exposure of rats

Ozone (O₃) exposure of humans and animals induces an inflammatory response in the lung, which is associated with macrophage stimulation, release of chemotactic agents, and recruitment of polymorphonuclear leukocytes (PMNs). This study was designed to investigate the functional aspects of the macrophages that impact inflammatory processes in the lung. Macrophages recovered by bronchoalveolar lavage (BAL) from rats exposed to purified air or 0.8 ppm O₃ were studied for their chemotactic activity, adhesive interactions with alveolar epithelial cells in culture, surface morphology, and surface expression of cell adhesion molecules. The macrophages isolated from O₃-exposed rats exhibited a greater motility in response to a chemotactic stimulus than the macrophages isolated from rats exposed to purified air. The macrophages from O₃-exposed animals also displayed greater adhesion when placed in culture with epithelial cells isolated from adult rat lung (ARL-14) than the macrophages from control rats. Both chemotactic motility and cell adhesion stimulated by O₃ exposure were attenuated when the macrophages were incubated in the presence of monoclonal antibodies to leukocyte adhesion molecules, CD11b, or epithelial cell adhesion molecules, ICAM-1. Flow cytometry revealed a modest increase in the surface expression of CD11b but no change in ICAM-1 expression in macrophages from O₃-exposed rats when compared to those from the air-exposed controls. The results demonstrate an alteration of macrophage functions following O₃ exposure and suggest the dependence of these functions on the biologic characteristics, rather than the absolute expression, of the cell adhesion molecules. © 1996 Wiley-Liss, Inc.     

Experimental Sepsis Impairs Humoral Memory in Mice

Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool’s development, which is not complete 8 weeks after secondary immunization.     

Bronchoalveolar eosinophilia in guinea pigs harboring inapparent infections of Paraspidodera uncinata

During the course of experiments examining the changes in cell populations in bronchoalveolar lavage (BAL) fluid in 3-11-wk-old guinea pigs, a marked increase in the numbers of eosinophils was observed in BAL fluid in untreated control animals from historical levels (observations made over the previous 2 yr) of 8.8 +/- 1.5% to levels greater than 16% and up to 44%. Repeated occurrence of this phenomenon in several different groups of guinea pigs that appeared clinically normal and the impact on our experimental studies led us to attempt to identify the cause of increased inflammatory cell numbers in these guinea pigs. Examination in 2 groups of animals of whole blood and lung tissue for the presence of bacteria or fungi revealed minor bacterial infections in one group but not the other, whereas both exhibited elevated eosinophil numbers. At necropsy, 41.7% and 60% of the animals in the 2 groups harbored the nematode Paraspidodera uncinata. Guinea pigs exhibiting eosinophil numbers in BAL fluid comparable to our historical levels were then inoculated with approximately 100 embryonated eggs of P. uncinata and developed elevated eosinophilia in BAL fluid compared to sham-inoculated animals (significant at 2 of the 3 examination times postinoculation). These findings suggest that P. uncinata is capable of causing changes in inflammatory cell populations in the lungs of guinea pigs and illustrate the importance of subclinical or inapparent infections in experimental design and interpretation.     

Caffeic acid phenethyl ester attenuates allergic airway inflammation and hyperresponsiveness in murine model of ovalbumin-induced asthma

Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis, which has several interesting biological properties, including antioxidant and anti-inflammatory; however, its anti-allergic effects are poorly understood. The objective of this study was to determine whether treatment with CAPE results in significant inhibition of asthmatic reactions in a mouse model. Mice sensitized and challenged with ovalbumin (OVA) had the following typical asthmatic reactions: an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness (AHR); the presence of tumor necrosis factor-alpha (TNF-alpha) and Th2 cytokines, including IL-4 and IL-5, in the BAL fluid; and the presence of allergen-specific IgE in the serum. Five successive intraperitoneal administrations of CAPE before the last airway OVA challenge resulted in significant inhibition of characteristic asthmatic reactions. We determined that increased generation of reactive oxygen species (ROS) by inhalation of OVA was diminished via the administration of CAPE in BAL fluid, as well as nuclear factor-kappaB (NF-kappaB) DNA binding activity. These findings indicate that oxidative stress may have a crucial function in the pathogenesis of bronchial asthma, and that CAPE may be useful as an adjuvant therapy for the treatment of bronchial asthma.     

Evidence that behavioral depression does not influence airway cell influx in allergic rats

This study was designated to evaluate the influence of behavioral depression on the airway leukocyte recruitment in allergic animals. To achieve this, total and differential cell counts in bronchoalveolar (BAL) fluid of ovalbumin (OVA)-sensitized and depressed rats was evaluated. Inescapable electric footshock, applied on day 0, 7 and 13 after OVA sensitization, was used as a model to induce depression. In both nondepressed and depressed groups, the number of total and differential cells (eosinophils and mononuclear cells) in BAL fluid was significantly larger in sensitized compared with non-sensitized animals. However, no statistical differences were found between these groups with respect to the number of total and differential leukocytes, irrespective of the day inescapable shock was applied. Thus, behavioral depression does not influence the pattern of cell infiltration into the airways of allergen-induced airway inflammation.     

Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment

The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.     

Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma

Background

Exposure to chlorine (Cl₂) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl₂-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.

Methods

Balb/C mice were exposed to Cl₂ gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl₂, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl₂ exposure.

Results

Mice exposed to Cl₂ had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl₂ exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl₂-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl₂ prevented lipid peroxidation in the lung. Following Cl₂ exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl₂ exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.

Conclusion

Our data show that the anti-oxidant DMTU is effective in attenuating Cl₂ induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress.     

Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma

Asthma is a chronic inflammatory disease of the airways characterized by airway remodeling, which includes changes in the extracellular matrix (ECM). However the role of the ECM in mediating these changes is poorly understood. Hyaluronan (HA), a major component of the ECM, has been implicated in asthma as well as in many other biological processes. Our study investigates the processes involved in HA synthesis, deposition, localization and degradation during an acute and chronic murine model of ovalbumin (OVA)-induced allergic pulmonary inflammation. Mice were sensitized, challenged to OVA and sacrificed at various time points during an 8-week challenge protocol. Bronchoalveolar lavage (BAL) fluids, blood, and lung tissue were collected for study. RNA, HA, protein and histopathology were analyzed. Analyses of lung sections and BAL fluids revealed an early deposition and an increase in HA levels within 24 h of antigen exposure. HA levels peaked at day 8 in BAL, while inflammatory cell recovery peaked at day 6. Hyaluronan synthase (HAS)1 and HAS2 on RNA levels peaked within 2 h of antigen exposure, while hyaluronidase (HYAL)1 and HYAL2 on RNA levels decreased. Both inflammatory cell infiltrates and collagen deposition co-localized with HA deposition within the lungs. These data support a role for HA in the pathogenesis of inflammation and airway remodeling in a murine model of asthma. HA deposition appears largely due to up regulation of HAS1 and HAS2. In addition, HA appears to provide the scaffolding for inflammatory cell accumulation as well as for new collagen synthesis and deposition.     

Adoptive transfer of acute lung injury

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.     

支气管哮喘伴发抑郁大鼠模型的建立

目的探讨建立支气管哮喘伴发抑郁动物模型的方法。方法选择Wistar大鼠,随机分为对照组与模型组,模型组采用卵蛋白(ovalbumin,OVA)激发法建立哮喘模型,在此基础上给予慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)28d,观察大鼠体质量、体征、肺组织结构、支气管肺泡灌洗液白细胞计数等变化,并用Open-field实验评价大鼠活动度和好奇心,通过糖水消耗实验评价大鼠快感缺乏与否。结果与对照组相比,模型组大鼠体质量增长明显缓慢(P0.05);肺组织呈哮喘样病理改变;支气管肺泡灌洗液白细胞总数、嗜酸粒细胞及淋巴细胞增多;Open-field实验,大鼠垂直活动得分、水平活动得分显著降低(P0.05);糖水消耗量明显减少(P0.05)。结论OVA激发复合CUMS可成功制备支气管哮喘伴发抑郁大鼠模型。     

Influence of refractory ceramic fibres - asbestos substitute - on the selected parameters of bronchoalveolar lavage 6 months after intratracheal instillation to W-rats

Industrial fibrous dusts are applied in many industrial branches and represent adverse factors in occupational and environmental area. Refractory ceramic fibers (RCFs) - amorphous alumina silicates - are used as one kind of asbestos substitutes. Because RCFs are relatively durable and some RCFs are respirable, they may present a potential health hazard by inhalation. The aim of present work was to find out the subchronic effect of RCFs on selected parameters of bronchoalveolar lavage (BAL) in W-rats, confirm the biopersistence of RCFs after 6 month instillation and contribute to the understanding of the pathomechanism of lung injury after fibrous dust exposure. Wistar rats were intratracheally instilled with 4 mg/animal of RCFs - exposed group and with 0.4 ml saline solution/animal - control group. Animals were sacrificed after 6 month exposure. Bronchoalveolar lavage (BAL) was performed and selected BAL parameters (mainly inflammatory and cytotoxic) were examined. After treatment with RCFs the following changes were observed: statistically significant increase in proportion of lymphocytes and polymorphonuclears as well as in % of immature alveolar macrophages (AM) and phagocytic activity of AM; statistically significant decrease in viability of AM and proportion of AM (from the differential cell count) in comparison with the control group. The results of this study indicated that RCFs even 6 months after intratracheal instillation very significantly changed the majority of examined BAL parameters. The presence of inflammatory and cytotoxic response in lung may signalize beginning or developing disease process.     

Bronchoalveolar lavage in an immunosuppressed rabbit model of invasive pulmonary aspergillosis

A rabbit model of invasive aspergillosis has been used to investigate the pathogenesis of Aspergillus infection in the immunosuppressed host. The animals received hydrocortisone daily and a single dose of cyclophosphamide 2 days prior to intratracheal instillation of conidia from Aspergillus fumigatus. Bronchoalveolar lavage (BAL) was performed in 3 infected and 2 control saline treated animals sacrificed on days 1, 2, 4, 7 and 10 following inoculation. Infective load within the lung was quantified using an assay for chitin which is an important component of fungal cell walls (in particular the hyphal cell wall) and is not present in vertebrate tissue. The total BAL white cell count did not discriminate between infected and saline treated animals and Aspergillus was cultured from one lavage specimen only. Infected animals developed a marked neutrophil alveolitis by day 2 in contrast to a near total absence of neutrophils in the lavages of the control animals. Phagocytosis of conidia by alveolar macrophages was prominent but did not prevent progressive infection as confirmed by measurement of lung chitin. This pattern of cellular response within the alveolar airspace reflects the complex nature of the response to Aspergillus infection in the immunosuppressed host.     

Hyperpnea-induced production of TBHP-initiated chemiluminescence in guinea pigs

Antioxidants attenuate hyperpnea-induced airway constriction. It was hypothesized that this type of airway constriction is closely related to reactive oxygen species (ROS). However, there is no direct evidence of an increase in ROS during or right after the course of hyperpnea. To detect ROS production induced by hyperpnea, forty one guinea pigs were divided into four groups: control; control with 95% O2-5% CO2; hyperpnea with 95% air-5% CO2; and hyperpnea with 95% O2-5% CO2. Three minutes following hyperpnea or at the equivalent time, we obtained bronchoalveolar lavage (BAL) and measured its chemiluminescence (CL) counts. In addition, hyperpnea with 95% O2-5% CO2 gas mixture was carried out and BAL was collected 3 minutes after the hyperpnea in an additional forty animals. We measured CL counts in BAL samples before and after the treatments of the following ROS scavenger(s) or saline in vitro: control (saline); superoxide dismutase (SOD); catalase; dimethylthiourea (DMTU); and SOD+catalase+DMTU. Hyperpnea with 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced significant increase in t-butyl hydroperoxide-initiated CL counts, which were inhibited by DMTU, catalase, or SOD in vitro. Our data suggest that hyperpnea with a 95% O2-5% CO2, but not with 95% air-5% CO2, gas mixture induced an increase in ROS production.     

Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background

Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone.

Methods

Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin.

Results

We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB₄ and nitrites while bone marrow cells increased the release of TNF-α and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-α, IL-10, LTB₄ and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF- α by cultured BAL cells and bone marrow cells.

Conclusions

Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed.     

Dietary phytoestrogens have anti-inflammatory activity in a guinea pig model of asthma

Phytoestrogens are a normal constituent of soy protein and have been shown to have anti-inflammatory activity in various in vitro and in vivo models. The present study was designed to determine if a diet enriched in the phytoestrogen isoflavones, genistin and daidzin, would alter the antigen-induced cellular infiltration, particularly eosinophilia, characteristic of a guinea pig model of asthma. Throughout the duration of the study, guinea pigs were maintained on a control diet (standard guinea pig chow) or the same diet enriched in isoflavones. The animals were placed on the diet 2 weeks prior to active sensitization with ovalbumin (OA). Three weeks after sensitization, animals were challenged with OA aerosol. The cellular infiltration into the lung and protein and red blood cells (RBC) in the bronchoalveolar lavage fluid (BAL) were determined 17 hr later. In animals maintained on the control diet, OA aerosol challenge resulted in the expected increase in eosinophils in both the BAL and the lung tissue, an increase in neutrophils in the BAL, and an increase in protein and the number of RBC in the BAL. In contrast, in animals maintained on the isoflavone diet, the OA-induced eosinophilia in the lung tissue was significantly attenuated. In addition, OA challenge caused a greater increase in BAL protein in animals maintained on the isoflavone diet compared with animals on the control diet. Our results indicated that a diet enriched in isoflavones results in reduced antigen-induced eosinophilia in the lung in the guinea pig model of asthma. However, this beneficial anti-inflammatory effect of dietary phytoestrogens is accompanied by a potentially detrimental increase in antigen-induced leakage of protein into the airspace.