SO2-induced enhancement of inhalative allergic sensitization: inhibition by anti-inflammatory treatment.

Epidemiological studies have shown a relationship between air pollution and allergic airway disease. In a previous study we have found that exposure to SO2 enhances allergic sensitization to inhaled ovalbumin (OA) in the guinea pig. We have now investigated the influence of pre-treatment with anti-inflammatory drugs on SO2-induced enhancement of allergic sensitization in this model. Four groups of 6 guinea pigs each were exposed to 5 ppm SO2 on 5 consecutive days over 8 h per day with intermittent inhalation of OA, while the air-control group was exposed to clean air and OA. During the period of SO2 exposure and sensitization three experimental groups were treated with indomethacin (group I), methylprednisolone (group M) and nebulized nedocromil sodium (group N), while the control group remained untreated. Guinea pigs were investigated for sensitization to OA by specific bronchial provocation tests using body plethysmographic measurement of compressed air (CA) and by measurement of specific antibody response in serum. While in the SO2-exposed control group 5 of 6 animals reacted to specific bronchial provocation testing (CA median 0.15 ml, range 0-0.175 ml), only 1 animal was sensitized in group M (CA 0 ml, 0-0.125, p < 0.05), whereas no bronchial reactions were seen in groups I and N (CA 0 ml, 0-0.05, p < 0.025). Specific IgG antibody titres increased in the control group (median 43 EU-->85 EU), but not in the treatment groups (medians group I 35 EU-->35 EU, group M 30-->35 EU, group N 64-->50 EU).(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of cells binding anti-IgE in the trachea and in the thoracic lymph nodes of ovalbumin-sensitized rats

We investigated in the present study the distribution of anti-IgE binding cells in the trachea and in the thoracic lymph nodes of ovalbumin (OA)-sensitized rats. Sensitization of the airways was induced through a single intratracheal injection of the antigen, and was controlled by recording in vitro the antigen-induced contraction of the tracheal muscle: 12 of 15 (80%) OA-injected rats had a demonstrable status of tracheal sensitization. An immunohistochemical method was used for the localization of the anti-IgE binding cells in cryostat and in Carnoy fixed tissue sections. Virtually no cell was found to bind anti-IgE in the tracheas or in the thoracic lymph nodes from control animals. Conversely, we found in OA-sensitized rats that: 1) numerous IgE plasma cells appeared in the medullary cords of the lymph nodes (not in the trachea); 2) in tracheal sections, IgE concentrated in the cytoplasm of subepithelial mast cells and of nonciliated rounded epithelial cells (possibly the so-called globule leukocytes), but few if any mast cells of the connective tissue bound the anti-IgE conjugates.     

Ovalbumin sensitization affects nonadrenergic noncholinergic relaxation response on guinea-pig tracheal smooth muscle]

We investigated the effects of anaphylactic challenge on nonadrenergic noncholinergic (NANC) relaxation response to electrical field stimulation (EFS) or to aminophylline in sensitized guinea pig tracheal smooth muscles. An anaphylactic challenge with ovalbumin (OA) reduced the relaxation response to EFS (20 V. 5 Hz. 300 pulse. duration 1 msec.), but the relaxation response to aminophylline was not affected by OA exposure. NG-monomethyl L-arginine, a nitric oxide (NO) synthesis inhibitor, reduced the relaxation response to EFS in the OA sensitized guinea pig. While the relaxation response to EFS on the sensitized guinea pig tracheal smooth muscle was significantly attenuated compared with that on the non-sensitized guinea-pig, there was no significant difference between the tracheal strip of OA challenge group and that of control group in sensitized guinea-pig under the existence of NO synthesis inhibitor. These results suggest that the attenuation of NANC relaxation response associated with sensitization plays an important role in airway hyperreactivity and is responsible for the decrease in NO amount.     

Repeated exposure to low levels of sulfur dioxide (SO2) enhances the development of ovalbumin-induced asthmatic reactions in guinea pigs.

BACKGROUND: Sulfur dioxide (SO2) is one of the major air pollutants. It is known to aggravate asthma symptoms in human beings, but few studies have focused on the effects of SO2 upon the development of bronchial asthma in animal models. OBJECTIVE: This study was undertaken to evaluate the role of SO2 upon the development of ovalbumin (OA)-induced asthmatic reactions in guinea pigs. METHODS: Guinea pigs were divided into four groups: (1) OA- and SO2-exposed group (n = 12), (2) SO2-exposed group (n = 12), (3) OA-exposed group (n = 11), and (4) saline-exposed group (n = 7). Guinea pigs of the first and second groups were exposed to 0.1 ppm SO2 for 5 hours a day on 5 consecutive days. Guinea pigs in the first and third groups inhaled 0.1% OA aerosols for 45 minutes a day on days 3, 4, and 5. One week after the sensitization procedure, all the guinea pigs underwent bronchial challenge with 1.0% OA aerosols, using unrestricted whole-body plethysmography. Bronchoalveolar lavage and histopathologic examination were performed 24 hours after the bronchial challenge. RESULTS: Increases in enhanced pause (Penh), as an index of airway obstruction, after the bronchial challenge was significantly higher in OA- and SO2-exposed group (group 1) than the other groups (P < .05, respectively). Eosinophil counts in bronchoalveolar lavage fluids were also significantly higher in group 1 than in the other groups (P < .05, respectively). Histopathologic findings of bronchial and lung tissue in the group 1 showed an infiltration of inflammatory cells, bronchiolar epithelial damage, and mucus and cell plug in the lumen, but no significant abnormalities were observed in the other groups. CONCLUSIONS: These results indicate that repeated exposure to low levels of sulfur dioxide may enhance the development of ovalbumin-induced asthmatic reactions in guinea pigs.     

BCG infection during pre-sensitization or even post-sensitization inhibits airway sensitivity in an animal model of allergic asthma

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.     

Effect of ozone exposure on allergic sensitization and airway inflammation induced by dendritic cells

BACKGROUND: Epidemiological studies suggest that ozone exposure is related to increased asthma symptoms. Dendritic cells (DCs) are the principal antigen-presenting cells in the airways. OBJECTIVE: We have examined whether ambient doses of ozone (100 ppb for 2 h) enhance allergic sensitization and/or airway inflammation in a mouse model. METHODS: C57BL/6 mice were sensitized to inhaled ovalbumin (OVA) by intratracheal instillation of OVA-pulsed DCs on day 0. Daily exposure to OVA aerosol on days 14-20 resulted in an eosinophilic airway inflammation, as reflected in bronchoalveolar lavage fluid and lung histology. In a first experiment, mice were exposed to ozone or room air immediately prior to and following sensitization. Subsequently, we tested the effect of ozone exposure during antigen challenge in DC-sensitized mice. RESULTS: Exposure to ozone during sensitization did not influence airway inflammation after subsequent allergen challenge. In contrast, in sensitized mice, challenge with OVA together with ozone (days 14-20) resulted in enhanced airway eosinophilia and lymphocytosis, as compared with mice exposed to OVA and room air (1.91 x 106 +/- 0.46 x 106 vs. 0.16 x 106 +/- 0.06 x 106 eosinophils/mL lavage fluid; P = 0.015; 0.49 x 106 +/- 0.11 x 106 vs. 0.08 x 106 +/- 0.03 x 106 lymphocytes/mL lavage fluid; P = 0.004). Ozone exposure without subsequent OVA exposure did not cause airway inflammation. CONCLUSION: Ozone exposure does not increase allergic sensitization but enhances antigen-induced airway inflammation in mice that are sensitized via the airways.     

Effects of ozone exposure on experimental asthma in guinea pigs sensitized with ovalbumin through the airway

As ozone (O3) is known to cause airway inflammation and hyperresponsiveness, we examined the effects of O3 exposure (1, 3, or 5 ppm, 2 h) on sensitization and provocation in guinea pigs sensitized with ovalbumin (OA) through the airway. In groups exposed to O3 before sensitization, 5 ppm increased the production of IgG1 antibodies and decreased the OA sensitization threshold from 0.01 to 0.002%. In those exposed before provocation, 1, 3, or 5 ppm of O3 decreased the OA provocation threshold from 0.5 to 0.02%, and this enhancement appeared to depend on airway hyperresponsiveness. We conclude that O3 exposure may play an important role in causing asthmatic attacks rather than enhancing allergic sensitization.     

Development of eosinophilic airway inflammation and airway hyperresponsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes.

We previously defined a role for B cells and allergen-specific immunoglobulins in the development of allergic sensitization, airway inflammation, and airway hyperresponsiveness (AHR), using a 10-d protocol in which allergen exposure occurred exclusively via the airways, without adjuvant. In the present protocol, normal and B-cell-deficient (microMt(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and challenged with OVA via the airways in order to examine the requirements for AHR with this protocol. T-cell activation (antigen-specific proliferative responses and Th2-type cytokine production) and eosinophil infiltration in the peribronchial regions of the airways, with signs of eosinophil activation and degranulation, occurred in both experimental groups. In contrast to the 10-d protocol, increased in vivo airway responsiveness to methacholine and in vitro tracheal smooth-muscle responses to electrical field stimulation were observed in both normal and B-cell-deficient mice, and these responses were inhibited by anti-interleukin (IL)-5 administration before airway challenge. These data show that IL-5, but not B cells or allergen-specific IgE, are required for eosinophil airway infiltration and the development of AHR following allergen/alum sensitization and repeated airway challenge with allergen. These results emphasize that the use of different sensitization and challenge protocols can influence the requirements for development of AHR.     

Reduced airway inflammation and remodeling in parallel with mucin 5AC protein expression decreased by s-carboxymethylcysteine, a mucoregulant, in the airways of rats exposed to sulfur dioxide

BACKGROUND: Human obstructive airway diseases are histopathologically characterized by inflammatory cell infiltration, goblet cell hyperplasia, and mucus hypersecretion in airways. We prepared a rat model of airway injury by exposure of sulfur dioxide (SO2) and then evaluated the effects of S-carboxymethylcysteine (S-CMC), a mucoregulant. METHODS: Rats were exposed to SO2 gas for 44 days and orally given S-CMC at 250 mg/kg, twice daily, from 21 to 44 days of exposure for histopathological and immunohistochemical evaluation. RESULTS: SO2 exposure induced inflammatory cell infiltration and mucus cell increase in rat airways. S-CMC treatment significantly decreased this inflammatory cell infiltration in proximal and peripheral airways. Morphometrically, SO2 exposure significantly increased the number of Alcian blue (pH 2.5)- and periodic acid-Schiff (AB/PAS)-positive cells in rat airways (11.8 x 10(-2) cell/nuclear profiles per micrometer basement membrane) compared to normal rat airways (1.6 x 10(-2) cell/nuclear profiles per micrometer basement membrane). S-CMC treatment significantly decreased the number of AB/PAS-positive cells (4.4 x 10(-2) cell/nuclear profiles per micrometer basement membrane, p < 0.01 vs. SO2-exposed rats). Immunohistochemically, SO2 exposure increased the expression of mucin 5AC (MUC5AC) protein in the airway epithelium of rats, but S-CMC treatment inhibited the increase. CONCLUSIONS: The increased mucus cells and MUC5AC protein expression seem associated with SO2-induced airway inflammation in rats. The fact that S-CMC suppresses airway inflammation and the increase in mucus cells and MUC5AC protein expression suggests that this mucoregulant may be advantageous in the treatment of inflammatory airway diseases with goblet cell hyperplasia.     

Sensitization to inhaled antigen by intratracheal instillation of dendritic cells

BACKGROUND: Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo. METHODS: Rats were immunized by intratracheal instillation of ovalbumin (OVA) -pulsed bone marrow-derived DCs or macrophages and exposed 10 days later to a 30-min aerosol of OVA on 3 consecutive days. Total and differential cell counts and flow cytometry on bronchoalveolar lavage (BAL) fluid, airway histology and serum OVA-immunoglobulin (Ig) E levels were analysed 24 h after the last exposure. RESULTS: As few as 2 x 104 OVA-DC induced sensitization to inhaled OVA. The secondary response to OVA-aerosol consisted of an antigen-specific increase in the number of bronchoalveolar mononuclear cells, activated CD4-positive alphabeta-TCR T lymphocytes, neutrophils and few eosinophils. Peribronchial and perivascular mononuclear cell infiltrates were seen on histological analysis. There was no production of systemic OVA-IgE. Bone marrow-derived macrophages did not induce sensitization. CONCLUSION: Delivering antigen to the respiratory tract via professional antigen-presenting DCs sensitizes for a secondary response to inhaled antigen leading to airway inflammation. This model will prove very useful for studying the early events of sensitization to inhaled antigen using the respiratory route.     

Chronic colonization of rat airways with Pseudomonas aeruginosa.

Colonization of the airways of rats by Pseudomonas aeruginosa was established by treating the animals with hexamethylphosphoramide (HMPA) and inoculating with P. aeruginosa. Male Sprague-Dawley rats were given tap water (controls) or HMPA in the drinking water at 2 or 4 mg/ml. The ciliated cells of the airway epithelium were denuded, and microulcerative lesions in the epithelium were induced in the HMPA-treated rats. After 2 weeks of treatment, the rats were inoculated by transoral intratracheal instillation with 5 X 10(7) CFU of P. aeruginosa obtained from a cystic fibrosis patient. Two weeks after inoculation, P. aeruginosa was cultured from the airways, and scanning and transmission electron microscopy showed bacilli adhering to or invading the injured airway epithelium. P. aeruginosa was present in tracheal and intrapulmonary tissue homogenates of 9% of the P. aeruginosa-inoculated control rats (n = 22) as compared with 61% of the 2-mg/ml (n = 18) and 65% of the 4-mg/ml (n = 20) HMPA-treated rats (P less than 0.05). No dose-response relationship was found between 2 and 4 mg of HMPA per ml and colonization. Contamination of 47% of all of the rats with Mycoplasma pulmonis, as indicated by a positive enzyme-linked immunosorbent assay for immunoglobulin G, had no discernible significant effect on colonization by P. aeruginosa. These results indicate that colonization of the rat airway by P. aeruginosa can be achieved experimentally by treating the animals with HMPA. This research supports the hypothesis that colonization by P. aeruginosa may occur in airways where the ciliated epithelium has been injured and epithelial lesions exist.     

Formaldehyde exposure enhances inhalative allergic sensitization in the guinea pig

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs ( n = 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgG1 (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group ( P < 0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P < 0.01; anti-OA-IgG1 13 vs. < 10 EU median, P < 0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig.     

Induction of airway hyperresponsiveness in allergic rats.

Brown-Norway rats (male) were sensitized with both dinitrophenylated-bovine serum albumin (DNP-BSA) and Bordetella pertussis simultaneously in order to induce airway hyperresponsiveness (AHR) as the first sensitization. At five days, DNP-BSA was inhaled as a booster into the airways under thiopental anaesthesia. At eight days, inhalation of antigen markedly increased the tracheal pressure (TP) in sensitized rats (11.9 +/- 1.6 cmH2O) and slightly increased TP in non-sensitized rats (1.1 +/- 0.4), the difference between the two groups being significant (p less than 0.001). Twenty-four hours after antigen challenge, the airway responsiveness to ACh in sensitized rats was markedly increased to about 4-fold as compared to that in non-sensitized rats. Inhalation of dinitrophenylated-ovalbumin failed to increase the airway responsiveness to ACh in rats sensitized with DNP-BSA, although a marked increase in TP was induced immediately after antigen challenge. We thus succeeded in preparing a model of AHR by employing a new procedure of sensitization.     

Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: development of tolerance using environmental antigens

BACKGROUND: Studies show that children in rural environments develop less asthma and allergic rhinitis than their urban counterparts. This may be a result, in part, of neonatal exposure to environmental antigens such as LPS and/or early exposure to allergens. OBJECTIVE: This study examined the effects of neonatal allergen and/or LPS exposure on subsequent immune responses to allergen. METHODS: Newborn mice were exposed to LPS and/or ovalbumin. At age 6 weeks, these animals were sensitized and challenged with ovalbumin, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. RESULTS: Animals exposed to LPS in the neonatal period developed T cells expressing CD25 and IL-10 on sensitization and challenge. They demonstrated abrogation of airway hyperresponsiveness and significant decreases in IL-13 from bronchoalveolar lavage fluid and in specific IgE. IL-4-expressing spleen cells were also significantly decreased. Mice exposed in the neonatal period to ovalbumin demonstrated airway hyporesponsiveness after subsequent ovalbumin sensitization and challenge and did not produce specific IgE. In contrast, these animals showed increases in IFN-gamma. Animals exposed to both LPS and ovalbumin developed a response characterized by IL-10 and IFN-gamma-expressing T cells. CONCLUSION: This suggests that mucosal antigen exposure in the neonatal period results in inhibition of allergic responses to environmental allergens. Early LPS exposure directs mucosal responses toward tolerance, whereas ovalbumin exposure follows the T(H)1-type response on subsequent sensitization. CLINICAL IMPLICATIONS: This study suggests that prevention of airways allergy may be best achieved by appropriate exposure of the airway mucosa early in life to environmental antigens.     

Role of IgE in the development of allergic airway inflammation and airway hyperresponsiveness – a murine model

The importance of IgE in airway inflammation and development of AHR in allergen-sensitized mice has been compared and contrasted in different models of sensitization and challenge. Using different modes of sensitization in normal and genetically manipulated mice after anti-IgE treatment, we have been able to distinguish the role of IgE under these different conditions. Striking differences in the three sensitization protocols were delineated in terms of the role of allergen-specific IgE, extent of eosinophilic airway inflammation, and development of AHR (Table 1). The highest levels of IgE and eosinophil infiltration (approximately 20-fold increases) were achieved after systemic sensitization with allergen (plus adjuvant) followed by repeated airway challenge. Passive sensitization with allergen-specific IgE followed by limited airway challenge induced a modest eosinophilic inflammatory response in the airways despite high levels of serum IgE. Exposure to allergen exclusively via the airways also resulted in a modest serum IgE response and a limited eosinophilic inflammatory response (approximately fourfold increases). Under all of these conditions, inhibition of IL-5-mediated eosinophilic airway inflammation was associated with attenuation of AHR. In contrast, the differences in the responses to the different modes of allergen exposure were associated with differences in the requirements for IgE in the development of AHR (Table 1). In the two models associated with mild eosinophil infiltration (passive sensitization and exclusive airway exposure), IgE was required for the development of AHR but did not substantially enhance airway inflammation on its own. However, IgE-allergen interaction was able to enhance T-cell function in vitro and induce T-cell expansion in vivo. In mice systemically sensitized and challenged via the airways, IgE (or IgE-mediated mast-cell activation) was not required for T-cell activation, eosinophilic inflammation and activation in the airways, or development of AHR. This was most clearly seen in B-cell-deficient and mast-cell-deficient, low-IgE-responder mouse strains (B6, B10) and in anti-IgE-treated high-IgEresponder mice (BALB/c). At the same time, we confirmed the importance of IgE in the induction of immediate-type hypersensitivity (mast-cell activation, immediate cutaneous hypersensitivity, passive cutaneous and systemic anaphylaxis). These differences were also highlighted by the means used to detect altered airway function. Passive sensitization and limited airway challenge or exclusive airway exposure to allergen over 10 days elicited changes in airway function that could be detected only in tracheal smooth-muscle preparations exposed to EFS. In contrast, systemic sensitization followed by repeated airway challenge resulted not only in changes in the contractile response to EFS but also in increased responsiveness to inhaled MCh. Thus, these results distinguish not only the differential involvement of IgE and eosinophil numbers but also their contribution to the readouts used to monitor airway function. Based on these studies, we conclude that IgE plays an important role in the development of airway inflammation and AHR under conditions in which limited IL-5-mediated eosinophilic airway infiltration is induced. In conditions where a robust eosinophilic inflammation of the airways is elicited, IgE (and IgE-mediated mast-cell activation) does not appear to be essential for airway inflammation and the development of AHR, detected as increased responsiveness to inhaled MCh. These findings reveal the potential importance of differential targeting in the treatment of allergic diseases with a predominance of IgE-mediated symptoms, e.g., allergic rhinitis and conjunctivitis, where anti-IgE may be an effective therapy, compared to those diseases with a predominant inflammatory component, e.g., AHR in atopic bronchial asthma, where anti-inflammatory or anti-IL-5 therapy may be more beneficial.     

Acidic mammalian chitinase is not a critical target for allergic airway disease

The expression of acidic mammalian chitinase (AMCase) is associated with Th2-driven respiratory disorders. To investigate the potentially pathological role of AMCase in allergic airway disease (AAD), we sensitized and challenged mice with ovalbumin or a combination of house dust mite (HDM) plus cockroach allergen. These mice were treated or not treated with small molecule inhibitors of AMCase, which significantly reduced allergen-induced chitinolytic activity in the airways, but exerted no apparent effect on pulmonary inflammation per se. Transgenic and AMCase-deficient mice were also submitted to protocols of allergen sensitization and challenge, yet we found little or no difference in the pattern of AAD between mutant mice and wild-type (WT) control mice. In a separate model, where mice were challenged only with intratracheal instillations of HDM without adjuvant, total bronchoalveolar lavage (BAL) cellularity, inflammatory infiltrates in lung tissues, and lung mechanics remained comparable between AMCase-deficient mice and WT control mice. However BAL neutrophil and lymphocyte counts were significantly increased in AMCase-deficient mice, whereas concentrations in BAL of IL-13 were significantly decreased compared with WT control mice. These results indicate that, although exposure to allergen stimulates the expression of AMCase and increased chitinolytic activity in murine airways, the overexpression or inhibition of AMCase exerts only a subtle impact on AAD. Conversely, the increased numbers of neutrophils and lymphocytes in BAL and the decreased concentrations of IL-13 in AMCase-deficient mice challenged intratracheally with HDM indicate that AMCase contributes to the Th1/Th2 balance in the lungs. This finding may be of particular relevance to patients with asthma and increased airway neutrophilia.     

The effects of contignasterol (IZP-94,005) on allergen-induced plasma protein exudation in the tracheobronchial airways of sensitized guinea - pigs in vivo

OBJECTIVE: To examine contignasterol (marine-derived) on allergen-induced plasma exudation in the tracheobronchial airways. MATERIAL: English shorthair guinea-pigs actively sensitized to ovalbumin. TREATMENT: 21 to 36 days after sensitization, contignasterol, budesonide or nedocromil and then ovalbumin (12 pmol) were superfused onto the tracheal mucosa (i. t.) of anaesthetized animals. METHODS: Tracer (125I-human serum albumin) was measured in tracheobronchial lavage. RESULTS: Thirty min after administration of contignasterol (100 and 200, but not 0.2 or 2.0 microg/kg), budesonide or nedocromil (200 microg/kg), the ovalbumin response (plasma exudate, microl) was significantly inhibited. The response was also inhibited 5 min after 200 microg/kg nedocromil but not after contignasterol or budesonide. CONCLUSIONS: Contignasterol was topically active and showed anti-inflammatory effects in the tracheobronchial airways in that it inhibited allergen-induced plasma protein exudation.     

Effect of capsaicin on bronchial reactivity and inflammation in sensitized adult rats

The involvement of tachykinins in the airway reactivity of ovalbumin (OA)-sensitized rats was studied by capsaicin (CAPS) treatment. In subcutaneously sensitized animals, the reactivity to both OA aerosol and serotonin given intravenously was decreased when CAPS was given after the sensitization period. No effects on the serum IgE and IgG antibody levels were seen in these animals. In contrast, when CAPS was given before the sensitization period, no effects were seen on the OA aerosol and serotonin reactivities. Immunohistochemical examination revealed that the Ia antigen expression in the bronchial epithelium was increased by both subcutaneous and aerosol sensitization. The CAPS treatment decreased this Ia antigen expression. Histological examination of mononuclear cells, mast cells and goblet cells revealed only small effects on the cell numbers by both the OA sensitization and the CAPS treatment. The results demonstrate a link between tachykinins, serotonin, the immune system and clinical lung reactivity. The mechanisms for this seem to be complex, since the timing of the CAPS treatment and antigen sensitization is crucial for the outcome.     

Effects of Vitamin E on airway responses and biochemical parameters in guinea pigs sensitized to ovalbumin

The effect of dietary supplementation with Vitamin E was studied in sensitized guinea pigs. After measurement of baseline airway reactivity and sensitization with ovalbumin, the animals were randomized into two groups: Group A, on a commercial feed and Group B, on dietary supplementation with oral Vitamin E (0.7 IU/kg). These were challenged with inhaled ovalbumin after 4 weeks. The following outcomes were studied: airway responses to ovalbumin inhalation, airway reactivity, sodium and calcium ion influx in isolated tracheal cells, Na+ K+ ATPase and Ca2+ ATPase activity in tracheal homogenate and plasma malonaldehyde. Sensitization increased airway reactivity in Group A but not in Group B. The tracheal cells of animals in Group B showed significantly lower rates of 45Ca and 22Na influx and lower activities of tracheal Na+ K+ ATPase and Ca2+ ATPase as compared to Group A. Plasma malonaldehyde was similar between two groups. We concluded that Vitamin E suppresses the increase in airway reactivity following sensitization and has membrane stabilizing actions.