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The effects of prednisolone, theophylline or salbutamol treatment were studied on leukocyte numbers in bronchoalveolar lavage (BAL) fluid taken 72 h after ovalbumin challenge in sensitized guinea pigs. Ovalbumin challenge resulted in an approximate 3-fold increase in the number of eosinophils in BAL fluid. This increase was significantly reduced by oral administration of prednisolone (59% inhibition with 10mg/ kg × 2) theophylline (56% with 50 mg/kg × 2) but not by salbutamol (10 mg/kg × 2). A comparison with the bronchodilator potency of the above drugs indicated that in guinea pigs salbutamol appears relatively selective as a bronchodilator, prednisolone is selective as an inhibitor of eosinophilia whilst theophylline displays a balance of both activities. Correspondence to: Dr. J. Llupiá, Department of Pharmacology, Laboratorios Almirall, Cardoner 68–74, E–08024 Barcelona (Spain) Introduction The clinical treatment of asthma includes the use of bronchodilators, such as salbutamol and/or anti-inflammatory agents, such as corticosteroids. In recent years the role of inflammation in asthma has been emphasized and the use of bronchodilators alone criticized on the grounds that they do not treat the underlying cause of the disease (i.e. inflammation). Theophylline, widely used in asthma treatment, was originally thougth to act predominantly via bron-chodilatation; however, recently there have been claims for an additional anti-inflammatory component of its antiasthma actions [1]. In order to study this possibility further we have compared the effects of theophylline with the corti-costeroid prednisolone on late phase airway leukocyte infiltration in a conscious guinea pig model of asthma [2]. We have also compared this activity of prednisolone, theophylline as well as salbutamol with their respective bronchodilator activities in anaesthetized guinea pigs. Methods Bronchodilatation Male Dunkin-Hartley guinea pigs (400–500 g) were maintained with free access to water but without food for 18 h. Drugs under study were then given orally 1 h before the animals were anaesthetized with urethane (1.4 g/kg, i.p.). In order to measure spontaneous respiratory flow and rate, a specially designed animal mask piece was used [3] connected to a pressure transducer. A jugular vein was cannulated to permit the administration of histamine (2 μg/kg, i.v. bolus) in order to induce bronchoconstriction. Histamine responses in drug-treated animals (oral administration) were compared to those in untreated control animals. ED50 values for drugs were calculated (doses causing 50% inhibition of bronchoconstriction). 294 D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /1 8/ 20 17 9 :4 1: 02 P M Gristwood/Llupiá/Fernández/Berga Table 1. Comparison between bronchodilator and leukocyte infiltration inhibitory potencies ofprednisolone, theophylline and salbutamol in guinea pigsPredniTheoSalbuta-solone phylline molBronchodilatationED50mg/kg, p.o. (n = 5) inactive at 40 35 7Leukocyte infiltrationED50mg/kg, p.o.(×2)(ní1⁄87) 7 40 > IOLeukocyte InfiltrationMale guinea pigs (450–500 g) were sensitized by the administration of aerosolized (Devilbiss35B nebulizer) ovalbumin (0.5 w/v in 0.9% saline) on two occasions separated by 7 days. Onday 14, animals were challenged by aerosolized ovalbumin under the cover of mepyramine(lOmg/kg, i.p.). Drug treatments, or vehicle, were given orally at both 2 h before and 6 h afterchallenge. Bron-choalveolar lavage (BAL) was performed 72 h after challenge with 2 × 4 mlvolumes of sterile saline. Numbers of eosinophils, neutro-phils, lymphocytes and macrophageswere evaluated. Total cell counts were performed using a Bürker Turk haemocytometer anddifferential counts carried out on cytocentrifuged preparations (Cytospin II) stained usingstaining foils (Sangodiff, Merck).ResultsIn untreated animals, ovalbumin challenge was associated with a significant increase in thenumber of eosinophils in the BAL fluid (8.3 ± 1.3 × 105 cells saline challenge, 2.1 ± 0.3×106cells ovalbumin challenge, n = 7). Significant changes in other cell numbers were not observedin these experiments.Prednisolone or theophylline treatment significantly inhibited the eosinophilia resulting fromovalbumin challenge whereas salbutamol had no significant effect at doses up to lOmg/kg × 2.Doses causing 50% inhibition (ED50 values) of the increase in eosinophil numbers are shown intable 1. Table 1 also compares the bronchodilator and leukocyte infiltration inhibitory potenciesof the drugs.ConclusionsOur results show that theophylline, like prednisolone, can significantly inhibit late phaseeosinophil infiltration into the lungs of ovalbumin sensitized-challenged guinea pigs. Acceptingthat lung inflammation in asthma is related to the infiltration of leukocytes including eosinophils[2, 4], our data support the concept that the antiasthmatic activity of theophylline includes ananti-inflammatory component. At an effective bronchodilator dose (lOmg/kg), salbutamol failedto significantly inhibit eosinophil influx. This result is in agreement with previously reporteddata for salbutamol in guinea pigs [5]. We can, therefore, conclude that in our tests salbutamolappears relatively selective as a bronchodilator, prednisolone is selective as an anti-inflammatoryagent whilst theophylline displays a balance of both anti-inflammatory and bronchodilatoractivities.ReferencesPauwels RA: New aspects of the therapeutic potential of theophylline in asthma. J Allergy ClinImmunol 1989;83:548–553. Downloadedby: 54.70.40.11-11/18/20179:41:02PM Hutson PA, Church MK, Clay TP, Miller P, Holgate ST: Early and late-phasebronchoconstriction after allergen challenge of nonanesthetized guinea pigs. Am Rev Respir Dis1988; 137: 548–557.Griffiths-Johnson DA, Nicholls PJ, McDermott M: Measurement of specific airway conductancein guinea pigs. A noninva-sive method. J Pharmacol Methods 1988;19:233–242.Durham SR, Loegering DA, Dunnette S, Gleich GJ, Kay AB: Blood eosinophils and eosinophil-derived proteins in allergic asthma. J Allergy Clin Immunol 1989;84:931–936.Hutson PA, Holgate ST, Church MK: The effect of cromolyn sodium and albuterol on early andlate phase bronchoconstriction and airway leukocyte infiltration after allergen challenge ofnonanesthetized guinea pigs. Am Rev Respir Dis 1988;138: 1157–1163. Downloadedby: 54.70.40.11-11/18/20179:41:02PM