Abstract
Representative glucocorticosteroids (GCS) and phosphodiesterase IV (PDE4) inhibitors were compared in several models of pulmonary inflammation ranging in severity. Lung tissue eosinophil peroxidase (EPO) levels rather than bronchoalveolar lavage fluid (BALF) EPO or eosinophil percentages were used to indicate eosinophil recruitment after intratracheal instillation of sephadex beads in rats or nebulized ovalbumin in sensitized guinea pigs. A single oral or intratracheal administration of a GCS was effective against mild and robust sephadex-induced eosinophilia whereas the PDE4 inhibitors evaluated appeared more effective in the milder sephadex models. The GCS were also more effective against sephadex-induced than ovalbumin-induced eosinophilia. The effectiveness of the GCS and PDE4 inhibitors improved when the severity of the ovalbumin-induced eosinophilia was decreased. Multiple day dosing also improved activity. These studies indicated that activity was influenced greatly by administration protocols, the severity of the inflammatory response and possibly the method used for estimating eosinophil recruitment.
Similar content being viewed by others
REFERENCES
BOUSQUET, J., P. CHANEZ, J. Y. LACOSTE, G. BARNEON, N. GHAVANIAN, I. ENANDER, P. VENGE, S. AHLSTEDT, J. SIMONY LAFONTAINE, P. GODARD, and F. B. MICHEL. 1990. Eosinophilic inflammation in asthma. N. Engl. J. Med., 323:1033-1039.
SEARS, M. R. 1993. The definition and diagnosis of asthma. Allergy, 48:12-16.
SZEFLER, S. J. 1991. Glucocorticosteroid therapy for asthma: clinical pharmacology. J. Allergy Clin. Immunol., 88:147-165.
LAITINEN, L. A., A. LAITINEN, and T. HAAHTELA. 1992. A comparative study of the effects of an inhaled corticosteroid, budesonide, and β2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a random, double-blind, parallel-group controlled trial. J. Allergy Clin. Immunol., 90:32-42.
SCHLEIMER, R. P. 1993. An overview of glucocorticoid anti-inflammatory actions. Eur. J. Clin Pharmacol., 45:S3-S7.
TINKELMAN, D. G., C. REED, H. S. NELSON, and K. P. OFFORD. 1993. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatrics, 92:64-77.
AGERTFT, T., and S. PEDERSEN. 1994. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Repir. Med., 88:373-381.
SANTING, R. E., C. G. OLYMULDER, K. VAN DER MOLEN, H. MEURS, and J. ZAAGSMA. 1995. Phosphodiesterase inhibitors reduce bronchial hyperreactivity and airway inflammation in unrestrained guinea pigs. Eur. J. Pharmacol., 275:75-82.
TEIXEIRA, M. M., R. W. GRISTWOOD, N. COOPER, and P. G. HELLEWELL. 1997. Phosphodiesterase(PDE)4 inhibitors: anti-inflammatory drugs of the future? Trends Pharmacol. Sci., 18:164-170.
KALLSTROM, L., R. BRATTSAND, U. LOVEGREN, E. SVENSJO, and K. ROEMPKE. 1985. A rat model for testing anti-inflammatory action in lung and the effect of glucocorticosteroids(GCS) in this model. Agents and Actions, 17:355-357.
SPICER, B. A., R. C. BAKER, P. A. HATT, S. M. LAYCOCK, and H. SMITH. 1990. The effects of drugs on sephadex-induced eosinophilia and lung hyper-responsiveness in the rat. Br. J. Pharmacol., 101:821-828.
LINSSEN, M. J., O. H. WILHELMS, and H. TIMMERMAN. 1991. Animal models for testing antiinflammatory drugs for treatment of bronchial hyperreactivity in asthma. Pharm. Weekbl. [Sci.], 13:225-237.
RAEBURN, D., S. L. UNDERWOOD, S. A. LEWIS, V. R. WOODMAN, C. H. BATTRAM, A. TOMKINSON, S. SHARMA, R. JORDAN, J. E. SOUNESS, S. E. WEBBER, and J-A. KARLSSON. 1994. Anti-inflammatory and bronchodilator properties of RP73401, a novel and selective phosphodiesterase type IV inhibitor. Br. J. Pharmacol., 113:1423-1431.
UNDERWOOD, D. C., C. J. KOTZER, S. BOCHNOWICZ, R. R. OSBORN, M. A. LUTTMANN, D. W. P. HAY, and T. J. TROPHY. 1994. Comparison of phosphodiesterase III, IV and dual III/IV inhibitors on bronchospasm and pulmonary eosinophil influx in guinea pigs. J. Pharmacol. Exp. Ther., 270:250-259.
BANNER, K. H., F. MARCHINI, A. BUSCHI, E. MORIGGI, C. SEMERARO, and C. P. PAGE. 1995. The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea pig airways. Pul. Pharmacol., 8:37-42.
BANNER, K., and C. L. PAGE. 1995. Acute and Chronic administration of phosphodiesterase inhibitors on allergen-induced pulmonary cell influx in sensitized guinea-pigs. Br. J. Pharmacol., 114:93-98.
HUGHES, B., D. HOWAT, H. LISLE, M. HOLBROOK, T. JAMES, N. GOZZARD, K. BLEASE, P. HUGHES, R. KINGABY, G. WARRELLOW, R. ALEXANDER, J. HEAD, E. BOYD, M. EATON, M. WALES, B. SMITH, R. OWENS, C. CATTERALL, S. LIMB, A. RUSSELL, R. ALLEN, M. MERRIMAN, D. BLOXHAM, and G. HIGGS. 1996. The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP-840, a novel stereo-selective inhibitor of phosphodiesterase type 4. Br. J. Pharmacol., 118:1183-1191.
HAMMERBECK, D. M., A. M. HUPPERTS, S. M. MCGURRAN, and G. W. GULLIKSON. 1997. Effects of several glucocorticosteroids on increases in total lung eosinophil peroxidase(EPO) levels and thymus involution in a sephadex-induced pulmonary inflammation model. Am. J. Respir. Crit. Care Med., 155:A623.
HAMMERBECK, D. M., S. M. MCGURRAN, A. M. HUPPERTS, J. OCHADA, G. COLICE, and G. W. GULLIKSON. 1997. Effects of several glucocorticosteroids on increases in total lung eosinophil peroxidase(EPO) levels following either systemic or intratracheal administration in sephadex-or ovalbumin-induced inflammatory models. Am. J. Respir. Crit. Care Med., 155:A623.
LAWRENCE, T. E., L. MILLECCHIA, and J. S. FEDAN. 1997. Fluticasone propionate and pentamidine isethionate reduce airway hyperreactivity, pulmonary eosinophilia and pulmonary dendritic cell response in a guinea pig model of asthma. J. Pharmacol. Exp. Ther., 284:222-227.
RYRFELDT, A., P. ANDERSSON, S. EDSBACKER, M. TONNESSON, D. DAVIES, and R. PAUWELS. 1982. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur. J. Respir. Dis., 63(suppl. 122):86-95.
HOLLIDAY, S. M., D. FAULDS, and E. M. SORKIN. 1994. Inhaled fluticasone propionate: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma. Drugs., 47:318-331.
DUNNILL, M. S. 1971. The pathology of asthma. In: Porter, R. and J. Birch, eds. The identification of asthma. Edinburgh: Church-Livingston: 35-46.
WARDLAW, A. J., S. DUNNETTE, G. J. GLEICH, J. V. COLLINS, and A. B. KAY. 1988. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Am. Rev. Respir. Dis., 137:62-69.
GLEICH, G. J. 1990. The eosinophil and bronchial asthma: current understanding. N. Engl. J. Med., 321:1517-1527.
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report. 1995. National Institutes of Health, National Heart, Lung, and Blood Institute.
GEORGITIS, J. W. 1999. The 1997 Asthma Management Guidelines and therapeutic issues relating to the treatment of asthma. Chest, 115:210-217.
FILLEY, W. V., K. E. HOLLEY, G. M. KEPHART, and G. J. GLEICH. 1982. Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma. Lancet., 2:11-16.
WOOLCOCK, A. J., K. YAN, and C. M. SALOME. 1988. Effect of therapy on bronchial hyperresponsiveness in the long-term management of asthma. Clin. Allergy, 18:165-176.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hammerbeck, D.M., Mcgurran, S.M., Radziszewski, P.L. et al. Effects of Several Glucocorticosteroids and PDE4 Inhibitors on Increases in Total Lung Eosinophil Peroxidase (EPO) Levels Following Either Systemic or Intratracheal Administration in Sephadexor Ovalbumin-induced Inflammatory Models. Inflammation 24, 317–329 (2000). https://doi.org/10.1023/A:1007092830169
Issue Date:
DOI: https://doi.org/10.1023/A:1007092830169