Mete Kaan BOZKURT, Baykal TÜLEK, Nalan AKYÜREK, Aysel KIYICI, Mehmet ÖZ, Banu BOZKURT

Comparison of the efficacy of prednisolone, montelukast, and omalizumab in an experimental allergic rhinitis model*

Aim: To compare the efficacy of prednisolone, montelukast, and omalizumab in reducing allergic symptoms and inflammation at tissue level in an experimental allergic rhinitis model. Materials and methods: Forty Sprague Dawley rats were randomized into 5 groups as naive (NS/NC), sensitized/challenged (S/C) by subcutaneous ovalbumin antigen injection, and montelukast-, prednisolone-, and omalizumab-treated groups. A nasal allergen challenge was performed every day from day 20 to day 26. The number of sneezes and nasal/eye rubbing movements, IL-4 and CysLT levels in serum, nasal and bronchoalveolar lavage fluids determined by ELISA, and histopathological findings of nasal mucosa, sinus, and lung tissues were compared. Results: All of the treatments significantly controlled the allergic symptoms of sneezing and nasal/eye rubbing (P < 0.05). IL-4 and CysLT levels on days 20 and 26 were significantly higher in the S/C group compared to the NS/NC group (P < 0.05). Montelukast significantly decreased serum and nasal IL-4 and CysLT levels (P < 0.05), prednisolone decreased nasal lavage IL-4 and CysLT levels (P < 0.05), and omalizumab lowered nasal lavage CysLT levels (P < 0.05). Conclusion: Prednisolone, montelukast, and omalizumab were found to be effective in controlling the allergic symptoms of allergic rhinitis and upper/lower airway inflammation in an experimental allergic rhinitis model.

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1. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, CanonicaGW, van Weel C et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008; 63 (Suppl. 86): 8160.
2. Poole JA, Rosenwasser LJ. The role of immunoglobulin E and immune inflammation: implications in allergic rhinitis. Curr Allergy Asthma Rep 2005; 5: 2528.
3. Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010; 125 (Suppl. 2): 7380.
4. Togias A. Rhinitis and asthma: evidence for respiratory system integration. J Allergy Clin Immunol 2003; 111: 117183.
5. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am 2004; 24: 1943.
6. Chervinsky P, Philip G, Malice MP, Bardelas J, Nayak A, Marchal JL, Bousquet J, Tozzi CA, Reiss TF. Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3 studies. Ann Allergy Asthma Immunol 2004; 92: 36773.
7. Mucha SM, deTineo M, Naclerio RM, Baroody FM. Comparison of montelukast and pseudoephedrine in the treatment of allergic rhinitis. Arch Otolaryngol Head Neck Surg 2006; 132: 16472.
8. Milgrom H, Fick RB, Su JQ, Reimann JD, Bush RK, Watrous ML, Metzger WJ. Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group. N Engl J Med 1999; 341: 196673.
9. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest 2004; 125: 137886.
10. Djukanović R, Wilson SJ, Kraft M, Jarjour NN, Steel M, Chung KF, Bao W, Fowler-Taylor A, Matthews J, Busse WW et al. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med 2004; 170: 58393.
11. van Rensen EL, Evertse CE, van Schadewijk WA, van Wijngaarden S, Ayre G, Mauad T, Hiemstra PS, Sterk PJ, Rabe KF. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy. 2009; 64: 7280.
12. Prieto L, Gutiérrez V, Colás C, Tabar A, Pérez-Francés C, Bruno L, Uixera S. Effect of omalizumab on adenosine 5-monophosphate responsiveness in subjects with allergic asthma. Int Arch Allergy Immunol 2006; 139: 12231.
13. Wu AY, Chik SC, Chan AW, Li Z, Tsang KW, Li W. Antiinflammatory effects of high-dose montelukast in an animal model of acute asthma. Clin Exp Allergy 2003; 33: 35966.
14. Henderson WR, Chiang GK, Tien Y, Chi EY. Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade. Am J Respir Crit Care Med 2006; 173: 71828.
15. Muz MH, Deveci F, Bulut Y, Ilhan N, Yekeler H, Turgut T. The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model. Exp Mol Med 2006; 38: 10918.
16. Roa J, Morikawa H, Crawford L, Baatjes A, Duong M, Denburg JA. The effects of montelukast on tissue inflammatory and bone marrow responses in murine experimental allergic rhinitis: interaction with interleukin-5 deficiency. Immunol 2007; 122: 43844.
17. Harrison S, Gatti R, Baraldo S, Oliani KL, Andre E, Trevisani M, Gazzieri D, Saetta M, Geppetti P. Montelukast inhibits inflammatory responses in small airways of the Guinea-pig. Pulm Pharmacol Therapeut 2008; 21: 31723.
18. Taylor IK, Shaw RJ. The mechanism of action of corticosteroids in asthma. Respir Med 1993; 87: 2617.
19. Narita S, Asakura K, Kataura A. Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms after antigen challenge in sensitized guinea pigs. Int Arch Allergy Immunol 1996; 109: 1616.
20. Busse WW. Leukotrienes and inflammation. Am J Respir Crit Care Med 1998; 157: S2103.
21. Henderson WR Jr, Tang LO, Chu SJ, Tsao SM, Chiang GKS, Jones F, Jonas M, Pae C, Wang H, Chi EY. A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model. Am J Respir Crit Care Med 2002; 165: 10816.
22. Shaw RJ, Fitzharris P, Cromwell O, Wardlaw AJ, Kay AB. Allergen-induced release of sulphidopeptide leukotrienes and LTB4 in allergic rhinitis. Allergy 1985; 40: 16.
23. Mizutani N, Nabe T, Imai A, Sakurai H, Takenaka H, Kohno S. Markedly increased nasal blockage by intranasal leukotriene D4 in an experimental allergic rhinitis model: contribution of dilated mucosal blood vessels. Jpn J Pharmacol 2001; 86, 170 82.
24. Underwood DC, Osborn RR, Newsholme SJ, Torphy TJ, Hay DW. Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig: modulation by the LTD4 receptor antagonist, pranlukast, or an interleukin-5 monoclonal antibody. Am J Respir Crit Care Med 1996; 154: 8507.
25. Shimizu T, Hirano H, Majima Y, Sakakura Y. A mechanism of antigen-induced mucus production in nasal epithelium of sensitized rats. A comparison with lipopolysaccharide-induced mucus production. Am J Respir Crit Care Med 2000; 161: 164854.
26. Holm AF, Godthelp T, Fokkens WJ, Severijnen EA, Mulder PG, Vroom TM, Rijnties E. Long-term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis. Clin Exp Allergy 1999; 29: 135666.
27. Jacobson MR, Juliusson S, Löwhagen O, Balder B, Kay AB, Durham SR. Effect of topical corticosteroids on seasonal increases in epithelial eosinophils and mast cells in allergic rhinitis: a comparison of nasal brush and biopsy methods. Clin Exp Allergy 1999; 29: 134755.
28. Braunstahl GJ, Fokkens WJ, Overbeek SE, KleinJan A, Hoogsteden HC, Prins JB. Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways. Clin Exp Allergy 2003; 33: 57987.
29. McCusker C, Chicoine M, Hamid Q, Mazer B. Site-specific sensitization in a murine model of allergic rhinitis: role of the upper airway in lower airways disease. J Allergy Clin Immunol 2002; 110: 8918.
30. Jeffery PK. Pathology of asthma. Br Med Bull 1992; 48: 2339. 31. Brozmanova M, Plevkova J, Bartos V, Plank L, Tatar M. Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs. J Physiol Pharmacol 2005; 56 (Suppl. 4): 2130.
32. Careau E, Sirois J, Bissonnette EY. Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats. Am J Respir Cell Mol Biol 2002; 26: 57986.