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Biomedical subjects

B E Skoogh

Publications and source records attributed to B E Skoogh.

At least 19 recordsLinked to original sources
PubMed1997

Different effects of a thromboxane mimetic on blood flow and plasma exudation in guinea pig airways and skeletal muscle.

Thromboxane A2 (TXA2) is a potent constrictor of both airway and vascular smooth muscle. In addition, plasma exudation is induced in the airways by a thromboxane mimetic (U-46619). Because plasma exudation is associated with a local vasodilatation and increased local blood flow, we hypothesized that the general vasoconstrictor effect of U-46619 would be weaker in the airways than in other vascular beds, perhaps resulting in increased local airway blood flow. We studied the effects of i.v. U-46619 on blood pressure, lung resistance as well as blood flow, plasma exudation in airways and leg skeletal muscle in guinea pigs. We found (1) i.v. U-46619 increases the systemic blood pressure, blood flow in tracheal mucosa but decreases blood flow in leg skeletal muscle; (2) i.v. U-46619 induces plasma exudation in the airways, but not in the leg skeletal muscle; (3) a positive relationship between blood pressure and tracheal blood flow as well as airway plasma exudation, a negative relationship between blood pressure and blood flow in leg skeletal muscle; (4) i.v. U-46619 significantly increases lung resistance. We conclude that i.v. U-46619 induces plasma exudation in airways but not in skeletal muscle, and that this plasma exudation is associated with the increased local blood flow, which in turn is caused by increased inflow pressure and redistribution of the total body blood flow to the airways.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

An intranasal glucocorticoid inhibits the increase of specific IgE initiated during birch pollen season.

BACKGROUND: Recent in vitro findings show that glucocorticoids in combination with IL-4 can induce the synthesis of IgE, indicating that glucocorticoids may promote allergy. OBJECTIVE: A double-blind, placebo-controlled study was performed to evaluate the effect of an intranasal glucocorticoid on the levels of birch pollen-specific IgE antibodies in serum from patients with allergic rhinitis. METHODS: Eighteen patients with allergic rhinitis received treatment with an intranasal glucocorticoid (beclomethasone dipropionate, 400 microg/day) or placebo for 5 weeks, starting from the beginning of the birch pollen season. Blood samples for anti-birch IgE evaluation were taken before treatment was initiated and at 2 and 5 weeks after the beginning of the study. RESULTS: The beclomethasone group (n = 9) had significantly lower symptom scores when compared with the placebo group (n = 9) (0.86 +/- 0.26 vs 2.79 +/- 0.76, p value = 0.01). Both the treatment group and the placebo group showed a trend of an increase in anti-birch IgE levels 2 weeks after the beginning of the treatment (from 33.1 +/- 13.1 kU/L to 44.9 +/- 20.9 kU/L in the beclomethasone group and from 53.2 +/- 18.9 kU/L to 64.1 +/- 22.1 kU/L in the placebo group). Treatment with beclomethasone returned anti-birch IgE levels to baseline by the end of the study, whereas in the placebo group the anti-birch IgE levels continued to increase (final values, 33.1 +/- 11.9 kU/L vs 72.6 +/- 23.2 kU/L, respectively). The change in IgE antibody levels in the placebo group was significantly higher than that in the beclomethasone group. No statistically significant changes in total IgE or soluble CD23 levels were detected. CONCLUSION: We conclude that treatment with an intranasal glucocorticoid initiated at the beginning of the pollen season inhibits the induced increase in specific IgE.

Administration, Intranasal↗
PubMed1997

Bronchial hyperresponsiveness, epithelial damage, and airway eosinophilia after single and repeated allergen exposure in a rat model of anhydride-induced asthma.

Bronchial hyperresponsiveness (BHR) and damage of the epithelium, as well as eosinophilia in the airway wall, induced by trimellitic anhydride (TMA) in sensitized brown Norway rats were studied. Rats were challenged once or seven times with aerosol of TMA conjugated to rat serum albumin (TMA-RSA) 3 weeks after intradermal TMA sensitization. Airway responsiveness (-log PC300 of acetylcholine i.v.) was measured 24 h after allergen challenge. Epithelial lesion and eosinophil infiltration in the airway walls were quantified under light microscopy, and TMA-specific IgE and IgG in serum were evaluated with ELISA. High levels of TMA-specific IgE and IgG were found in all rats in the sensitized groups compared to nonsensitized groups (P < 0.001). Repeated allergen challenges of 0.03% TMA-RSA for 7 consecutive days enhanced the level of TMA-specific IgG, compared to single challenge (P < or = 0.05). Single allergen challenge of 0.3% TMA-RSA had a nonsignificant tendency to produce BHR in sensitized rats compared to nonsensitized rats (P = 0.06). However, repeated allergen challenges (0.003% and 0.03% TMA-RSA for 7 consecutive days) produced significant BHR in sensitized rats (P < 0.05). Furthermore, repeated low-dose (0.003%) TMA-RSA challenge produced more BHR than a 10 times higher single dose (0.03%) (P < 0.05). Slight damage of the airway epithelium was seen in sensitized and repeat-challenged groups. However, bronchial eosinophilia was found in the sensitized and single-challenged groups, but not in nonsensitized nonchallenged, and sensitized repeat-challenged groups (P < 0.005). We conclude that the brown Norway rat can be sensitized with TMA, and that repeated low-dose allergen challenges produce slight epithelial damage and BHR which is independent of ongoing eosinophilia in the airway wall.

Animals↗
PubMed1997

Development of antigen-specific IgE after sensitisation with trimellitic anhydride in rats is attenuated by glucocorticoids and cyclosporin A.

BACKGROUND: Trimellitic anhydride (TMA) is a low-molecular-weight compound capable of inducing occupational asthma in man. We have characterized the TMA-induced antibody responses in Brown-Norway rats (BNR) and evaluated the effects of treatment with the glucocorticoid betamethasone or with cyclosporin A (CsA) on this response. METHODS: Animals were sensitised by two intradermal injections of 0.1 ml TMA suspended in corn oil, and development of specific antibodies was assessed using ELISA. RESULTS: Both IgE and IgG anti-TMA antibodies started to rise between weeks 1 and 3 after immunisation, reached their highest levels 7 weeks after sensitisation with 3% of TMA and then started to decline. Betamethasone and CsA given orally over the time of sensitisation (8 days in total) inhibited the development of specific IgE and IgG anti-TMA antibodies. Betamethasone given 10-17 days after sensitisation attenuated the IgE and IgG antibody responses as well while treatment with CsA after sensitisation had no effect on the production of specific antibodies. Levels of total IgE and IgG were not affected except for a small decrease in total IgE using medium-dose betamethasone after sensitisation. CONCLUSION: We conclude that TMA-sensitised BNR develop specific IgE and IgG anti-TMA antibodies, and that glucocorticoids and CsA attenuate this response.

Allergens↗
PubMed1997

8-Epi-PGF2alpha induces airflow obstruction and airway plasma exudation in vivo.

8-Epi-prostaglandin F2alpha (8-epi-PGF2alpha) is an F2-isoprostane formed mainly via noncyclooxygenase pathways in vivo. We investigated whether 8-epi-PGF2alpha has any effect on airflow obstruction and plasma exudation in vivo. Airflow obstruction was quantified by measuring lung resistance (RL) in anesthetized and ventilated guinea pigs, and plasma exudation was quantified by the Evans Blue dye method (20 mg/kg intravenously). Intratracheal instillation of 8-epi-PGF2alpha (1 nmol or 10 nmol) caused dose-related increases in RL. Furthermore, the higher dose of 8-epi-PGF2alpha produced Evans Blue dye extravasation in main bronchi and intrapulmonary airways. A prostanoid TP-receptor antagonist, BAY u3405 (1 mg/kg intravenously), abolished the airway effects of 8-epi-PGF2alpha (10 nmol). A thromboxane A2 (TxA2) synthase inhibitor, OKY-406 (30 mg/kg intravenously), significantly attenuated these effects of 8-epi-PGF2alpha (10 nmol). The level of TxB2, a stable TxA2 metabolite, increased in bronchoalveolar lavage fluid (BALF) after 8-epi-PGF2alpha instillation. We conclude that 8-epi-PGF2alpha causes airflow obstruction and plasma exudation in vivo. This effect may be mediated primarily via prostanoid TP-receptors, and a secondary generation of TxA2 may be involved in part of the airway responses in 8-epi-PGF2alpha in the guinea pig.

Airway Obstruction↗
PubMed1996

Inflammatory responses in skin and airways after allergen challenge in brown Norway rats sensitized to trimellitic anhydride.

Trimellitic anhydride (TMA) is a low-molecular-weight compound which causes occupational allergy. Brown Norway rats were sensitized to TMA injected intradermally (0.3% TMA suspended in oil). Three weeks later, we examined responses to either free TMA injected intradermally, or TMA conjugated to rat serum albumin (TMA-RSA) given by inhalation (0.5%, nebulized for 15 min). Twenty-one days after the sensitization, Evans blue dye was given i.v. (20 mg/kg), and extravasation of dye in skin was measured 30 min after oil or TMA injections (0.03-10% in oil). In a separate series of experiments, we evaluated the accumulation of eosinophils in the skin after single and repeated injections of TMA (0.03-0.3%). The injection sites were removed and fixed in formalin 18-24 h after the last injection. In a third series of experiments, we evaluated the effects of airway exposure to TMA-RSA (0.5% in 0.9% saline) on the accumulation of eosinophils in the bronchial wall counted with quantitative light microscopy. Intradermal injections of free TMA caused a dose-dependent increase of Evans blue dye extravasation which was significantly higher in sensitized animals than in controls. Skin histology revealed a significant and dose-dependent increase in eosinophils after repeated TMA injections in sensitized animals. Exposure to aerosolized TMA-RSA caused a significant increase of eosinophils in the bronchial wall of sensitized rats compared with nonsensitized rats. Sensitized animals showed significantly higher levels of specific IgG and IgE. We conclude that brown Norway rats can be used as a model of TMA-induced allergic inflammation, mimicking occupational asthma.

Administration, Cutaneous↗
PubMed1996

Extent of salmeterol-mediated reassertion of relaxation in guinea-pig trachea pretreated with aliphatic side chain structural analogues.

1. Salmeterol is a potent, selective and long acting beta 2-adrenoceptor agonist. In vitro, salmeterol exerts 'reassertion' relaxation of airways smooth muscle. Reassertion relaxation refers to the capacity of salmeterol to cause repeated functional antagonism of induced contraction when airway smooth muscle is intermittently exposed to, then washed free from, beta-adrenoceptor antagonists such as sotalol. The mechanism(s) underlying reassertion relaxation are unknown but may relate to high affinity binding of the long aliphatic side chain of salmeterol to an accessory site, distinct from the agonist recognition site, in or near the beta 2-adrenoceptor (exosite binding hypothesis). 2. In order to test the exosite hypothesis, three pure analogues of salmeterol, each exactly preserving the molecular structure of the aliphatic side chain but with zero or low efficacy at the beta 2-adrenoceptor were synthesized. The effect of pre-incubating guinea-pig tracheal smooth muscle with these analogues on salmeterol-induced reassertion relaxation was determined. 3. Computer Assisted Molecular Modelling of these molecules revealed that each of them exactly preserved the low energy linear conformation of the aliphatic side chain of salmeterol. Measurement of lipophilicity (octanol:water partition coefficient; log P) and direct partition into synthetic membranes (membrane partition coefficient; Kpmem) showed that all compounds had high affinity for lipids and membranes. In particular the biophysical properties of CGP 59162 (log P 1.89, Kpmem 16500) were very similar to salmeterol (log P 1.73, Kpmem 16800). 4. Two of the analogues, CGP 54103 and D 2543 (1 microM), which are structural mimics of the side chain of salmeterol, differing slightly in their length, did not prevent either the initial relaxation induced by salmeterol (0.1 microM) or the reassertion relaxation; however, it was not possible to determine whether either of these molecules occupied the beta 2-adrenoceptor. 5. The third analogue, CGP 59162, which has the substituents on the active saligenin head group of salmeterol in transposed positions, itself exerted a weak beta 2-adrenoceptor-mediated relaxation antagonized by ICI 118551 (beta 2-selective antagonist) but not CGP 20712 (beta 1-selective antagonist) and, at higher concentrations CGP 59162 caused reassertion relaxation suggesting that it may occupy and activate the beta 2-adrenoceptor in a manner analogous to salmeterol. 6. CGP 59162, at concentrations up to ten fold molar excess, did not prevent or reduce salmeterol-induced reassertion relaxation. 7. In conclusion these data are not consistent with the existence of a distinct 'exosite' recognising the aliphatic side chain of salmeterol mediating reassertion.

Adrenergic beta-Agonists↗
PubMed1996

U46619 (a thromboxane A2 mimetic) induces airflow obstruction and airway plasma extravasation in the guinea pig: the role of histamine, cyclooxygenase metabolites, leukotrienes and PAF.

The aim of the present study was to characterize the airway effects of U46619, a stable thromboxane A2 mimetic, instilled into the trachea of guinea pigs in vivo, and to investigate the role of different mediators in these effects. The airflow obstruction was evaluated by measurement of airway insufflation pressure (P1) and plasma extravasation by quantification of Evans Blue dye (EBD) in airways. U46619, given as a single dose to each animal (1 pmol-10 nmol), caused a dose-dependent increase in P1 and extravasation of EBD. The threshold dose required to induce an increase in P1 was 30 times lower than the threshold dose necessary to evoke EBD extravasation. The role of inflammatory mediators was studied when 10 pmol (inducing only the increase in P1) or 10 nmol (inducing the increase in both P1 and EBD extravasation) of U46619 was administered. The effects of both doses of U46619 were abolished by ICI192,605, an antagonist of prostanoid receptor for thromboxane A2 (0.5 mg/kg i.v.). The airflow obstruction induced by 10 nmol of U46619 was potentiated by indomethacin, a cyclo-oxygenase inhibitor (10 mg/kg i.v.). EBD extravasation induced by 10 nmol U46619 was attenuated by BW70C (6 mg/kg i.v.), a selective 5-lipoxygenase inhibitor, by ICI198,615 (0.5 microgram/kg i.v.), a leukotriene D4/E4 receptor antagonist and by WEB2086 (1 mg/kg i.v.) a platelet-activating factor receptor antagonist. Pyrilamine (2 mg/kg i.v.), a histamine H1 receptor antagonist, did not have any influence on U46619-induced airway effects. We conclude that U46619 possesses a higher potency in the induction of airflow obstruction than in the induction of plasma extravasation and that U46619-induced plasma extravasation may be partly mediated via leukotrienes and platelet-activating factor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction.

The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects are associated with a local thromboxane A2 release.

Airway Obstruction↗
PubMed1995

Airway effects of salmeterol in healthy individuals.

The long-acting beta 2-agonist salmeterol has been shown in several in vitro studies to produce non-beta-mediated relaxant effects. The aim of the present study was to investigate whether these effects have any relevance in humans in vivo. Thirteen healthy individuals were studied in a randomized, double-blind, cross-over study on five separate days. The subjects were pre-treated orally with either propranolol 400 mg in order to block beta-adrenoceptor mediated effects or placebo. Two hours after drug intake, three increasing doses of salmeterol (25 + 50 + 100 micrograms), salbutamol (100 + 200 + 400 micrograms) or placebo were given from matched meter dose inhalers at 1-h intervals between doses. Specific airway conductance (sGAW) was measured in a body plethysmograph at the beginning of the experiment and 30 and 60 min after each inhaled dose of the beta-agonists. Salmeterol and salbutamol produced the same maximal increase in sGAW and had the same area under the dose-response curves. Pre-treatment with propranolol totally inhibited the effect of both drugs. In conclusion, salmeterol at clinically used doses did not produce any non-beta-mediated bronchodilating effect in normal individuals, measured as sGAW. Salmeterol and salbutamol showed the same efficacy but salmeterol was four times more potent than salbutamol.

Administration, Inhalation↗
PubMed1995

Induction of nitric oxide synthase in a model of allergic occupational asthma.

We have studied the induction of nitric oxide during late allergic responses, using a guinea pig model of trimellitic anhydride (TMA)-induced airway allergy. TMA is a low molecular weight chemical which can cause occupational asthma. The activity of nitric oxide synthase (NOS) was investigated by the detection of 3H-labeled citrulline formation from 3H-labeled arginine. In sensitized animals, challenge with TMA conjugated to guinea pigs albumin (TMA-GPSA) increased the activity of Ca(2+)-independent NOS (inducible NOS; iNOS) in lung and bronchial tissues at 15-17 h after challenge compared to nonsensitized animals. The induction of iNOS activity was associated with an associated with an increased level of nitrite, an end metabolite of the l-arginine-NO pathway, in bronchoalveolar lavage fluid. In contrast to iNOS, the activity of Ca(2+)-dependent NOS (constitutive NOS; cNOS) was not affected by the allergen challenge. These results demonstrate that iNOS in bronchial tissue is induced late after allergen challenge in sensitized guinea pig.

Allergens↗
PubMed1995

Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea.

1. In the present study, the inhibitory effects of the selective beta 2-adrenoceptor agonists, salmeterol, formoterol and salbutamol, have been investigated on contractions of ferret trachea induced both by endogenous and exogenous acetylcholine. The aim of the study was to evaluate quantitative and/or qualitative differences in response which may indicate both pre- and post-junctional sites of action. The non-selective beta-antagonist, sotalol, was used to estimate beta-adrenoceptor involvement. 2. Isometric tension was measured in ferret isolated tracheal strips. The inhibitory effects of the drugs were studied on tonic contractions induced by pre-junctional activation with electrical field stimulation (EFS) (2 Hz, 700 mA) or post-junctional activation with exogenous acetylcholine (ACh) (0.5 microM, about EC80), giving a similar degree of smooth muscle response. 3. Concentration-response experiments were performed with formoterol (0.3 nM-0.3 microM) and salmeterol and salbutamol (10 nM-10 microM). The experiments ended with the addition of sotalol (10 microM). 4. All three beta-agonists inhibited the contractions in a concentration-dependent manner. Salbutamol, formoterol and salmeterol inhibited the EFS-induced contractions by 66(8)%, 105(5)% and 103(8)% (mean(s.e. mean)) respectively. ACh-induced contractions were inhibited by 37(6)%, 72(11)% and 33(8)%. Theophylline (10 nM-3 mM) inhibited the contractions to the same degree. 5. beta-Adrenoceptor blockade by sotalol significantly antagonized the inhibitory effects of salbutamol and formoterol on both EFS- and ACh-induced contractions. The effect of salmeterol on ACh-induced contraction was also significantly antagonized, whereas the inhibition of EFS-induced contraction was virtually unaffected. 6. In conclusion, salbutamol, salmeterol and formoterol produced greater inhibitory effects in preparations contracted by EFS than in preparations contracted by exogenously-added ACh. In the case of formoterol and salbutamol, the effects on both levels are most probably due to beta-adrenoceptor stimulation, whereas for salmeterol the dominant pre-junctional effect is probably not mediated via beta-adrenoceptors. This non-beta-mediated effect could represent an additional relaxant mechanism for salmeterol.

Acetylcholine↗
PubMed1995

Airway responses following intradermal sensitization to different types of allergens: ovalbumin, trimellitic anhydride and Dermatophagoides farinae.

Sensitization of guinea pigs by intradermal injections of the occupational allergen trimellitic anhydride (TMA) in oily vehicle has been shown to be very reproducible. We studied the effect of intradermal sensitization with ovalbumin (OA) in oily vehicle on immune and airway responses in guinea pigs. We also compared airway responses to trimellitic anhydride or Dermatophagoides farinae (DF; mite) with those to OA in guinea pigs intradermally sensitized to respective allergens. Three to four weeks after sensitization, the animals were challenged with intratracheal instillation of these allergens. Intradermal injections with OA developed dose-dependently specific IgG1 antibodies to OA demonstrated by ELISA. In animals sensitized with different doses of OA in corn oil vehicle, a challenge with OA induced a reversely dose-dependent airflow obstruction and airway plasma exudation. In contrast, animals sensitized with OA in saline vehicle had dose-dependent airway responses to OA. Challenge with OA caused an immediate peak and subsequently persistent airflow obstruction, whereas this response to either TMA guinea pig serum albumin or Df was slowly progressive in animals sensitized to respective allergens. The animals sensitized to TMA or Df may show a different profile of airway responses following the challenge compared to OA. Intradermal sensitization may be a valuable method of sensitization for the development of an animal model of airway allergy to different types of allergens, including chemicals or mites.

Allergens↗
PubMed1994

Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig.

Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 +/- 3 g: 2 weeks) and adult guinea pigs (512 +/- 5 g: 11 weeks). In the same animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in RL in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in RL did not change with age (leukotriene D4 > U-46619 > acetylcholine). In immature animals, the peak RL after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Treatment with cyclosporin A during sensitization with trimellitic anhydride attenuates the airway responses to allergen challenge three weeks later.

The present studies examined the effects of oral treatment with cyclosporin A, betamethasone or azelastine administered over the time of sensitization with trimellitic anhydride on allergen-induced airway responses, compared to those of control animals given corn oil alone. Drugs were given for 8 days. The animals were sensitized with trimellitic anhydride (0.1 ml of 0.3% w/v) in corn oil given intradermally on days 4 and 5 of drug treatment. Three to four weeks after sensitization with free trimellitic anhydride, the animals were anesthetized, tracheostomized and challenged with trimellitic anhydride conjugated to guinea pig serum albumin (trimellitic anhydride-guinea pig serum albumin; 0.5%; 50 microliters) instilled via the airway route. In the same animal, we measured both lung resistance (RL) to monitor airflow obstruction, and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. In control animals, instillation of trimellitic anhydride-guinea pig serum albumin into the tracheal lumen caused a slowly progressing increase in RL over the observation period (6 min), in addition to extravasation of Evans Blue dye at all airway levels. In animals treated with 50 mg/kg of cyclosporin A, both the allergen-induced increase in RL and extravasation of Evans Blue dye in intrapulmonary airways were significantly attenuated. However, neither betamethasone nor azelastine significantly affected these responses. We conclude that cyclosporin A may influence the immune system in the guinea pig during the induction of allergy, thus leading to attenuation of allergen-induced airway obstruction at later time points.

Administration, Oral↗