Changes in Upper and Lower Airway Inflammation Following Administration of Mometasone Furoate in Allergen-Challenged Brown Norway Rats

Abstract

Background:

In order to assess the antiinflammatory effects of mometasone furoate (CAS 83919-23-7, Sch 32088, MF) in an animal model of allergic airway disease, nasal inflammation (total cell count [TCC] in nasal lavage [NL]) and pulmonary inflammation (total and differential cell count) in bronchoalveolar lavage (BAL), forced vital capacity (FVC) and peak expiratory flow (PEF) were measured in ovalbumin (OVA)-sensitized and -challenged Brown Norway rat following pretreatment with MF or vehicle.

Methods:

Rats were sensitized twice over 14 days with OVA and placed into 1 of 4 protocols: Group 1: intranasal (i. n.) MF (0.001–100 µg/mL) or vehicle once daily for 3 days; Group 2: intratracheal (i. t.) MF (0.001 −0.3 mg/kg i. t.) or vehicle, one dose; Group 3: i. t. MF (0.1–1 mg/kg, i. t.) or vehicle, one dose; Group 4: nose-only inhalation (n. o. i.) of dry powder MF (estimated pulmonary deposition of MF, 1.4, 4.1, and 13.3 µg/kg) or vehicle, once daily for 3 days. Group 1 was challenged with i. n. OVA (1%) 2 h after last treatment dose. Groups 2–4 were challenged with aerosolized OVA (1%) 5 h after treatment. Assessments were performed 24 h post-challenge (Group 1: NL; Group 2: BAL; Group 3 and 4: FVC and PEF).

Results:

Rats treated with MF demonstrated significant and dose-dependent improvements in nasal inflammation and lung function compared to those treated with vehicle; normalization of these markers to levels consistent with non-sensitized animals were noted at the highest MF doses. Improvements in lung function were similar with i. t. and n. o. i. administration. Pulmonary infiltration of total cells and eosinophils was significantly attenuated after one dose of i. t. MF (0.003–0.3 mg/kg).

Conclusion:

In this established model of allergic airway disease, MF significantly attenuated cellular infiltration in the upper and lower airways and normalized lung function following allergen provocation.

Key words

Antiallergic agents - CAS 83919-23-7 - Corticosteroids - Mometasone furoate, antiinflammatory effects, allergen-challenged rat - Sch 32088

• References

• 1 Rowe-Jones JM. The link between the nose and lung, perennial rhinitis and asthma-is it the same disease?. Allergy. 1997; 52 (36 Suppl) 20-8
• 2 Rimmer J, Ruhno JW. Rhinitis and asthma: united airway disease. Med J Aust. 2006; 185: 565-7
• 3 Lim YS, Won TB, Shim WS, Kim YM, Kim JW, Lee CH et al. Induction of airway remodeling of nasal mucosa by repetitive allergen challenge in a murine model of allergic rhinitis. Ann Allergy Asthma Immunol. 2007; 98: 22-31
• 4 Gomez E, Corrado OJ, Baldwin DL, Swanston AR, Davies RJ. Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man. J Allergy Clin Immunol. 1986; 78 (4 Pt 1) 637-45
• 5 James A, Ryan G. Testing airway responsiveness using inhaled methacholine or histamine. Respirology. 1997; 2: 97-105
• 6 Sterk PI, Bel EH. Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing. Eur Respir J. 1989; 2: 267-74
• 7 Nakajima H, Iwamoto I, Tomoe S, Matsumura R, Tomioka H, Takatsu K et al. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis. 1992; 146: 374-7
• 8 Naclerio RM. Allergic rhinitis. N Engl J Med. 1991; 325: 860-9
• 9 Ciprandi G, Pronzato C, Ricca V, Passalacqua G, Bagnasco M, Canonica GW. Allergen-specific challenge induces intercellular adhesion molecule 1 (ICAM-1 or CD54) on nasal epithelial cells in allergic subjects. Relationships with early and late inflammatory phenomena. Am J Respir Crit Care Med. 1994; 150: 1653-9
• 10 Masuyama K, Jacobson M, Rak S, Meng Q, Sudderick RM, Kay AB et al. Topical glucocorticosteroid (fluticasone propionate) inhibits cells expressing cytokine mRNA for inter-leukin-4 in the nasal mucosa in allergen-induced rhinitis. Immunology. 1994; 82: 192-9
• 11 Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001; 108 (1 Suppl) S2-8
• 12 Fujitani Y, Trifilieff A. In vivo and in vitro effects of SAR 943, a rapamycin analogue, on airway inflammation and remodeling. Am J Respir Crit Care Med. 2003; 167: 193-198
• 13 Xu KF, Vlahos R, Messina A, Bamford TL, Bertram IF, Stewart AG. Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia. J Appl Physiol. 2002; 93: 1833-40
• 14 McCormack PL, Plosker GL. Inhaled mometasone furoate: A review of its use in persistent asthma in adults and adolescents. Drugs. 2006; 66: 1151-68
• 15 Kung TT, Jones H, Adams GK, 3rd Umland SP, Kreutner W, Egan RW. et al. Characterization of a murine model of allergic pulmonary inflammation. Int Arch Allergy Immunol. 1994; 105: 83-90
• 16 Uller L, Lloyd CM, Rydell-Törmänen K, Persson CG, Erjefält JS. Effects of steroid treatment on lung CC chemokines, apoptosis and transepithelial cell clearance during development and resolution of allergic airway inflammation. Clin Exp Allergy. 2006; 36: 111-21
• 17 Greiff L, Anderssonj M, Svensson C, Linden M, Wollmer P, Brattsand R et al. Effects of orally inhaled budesonide in seasonal allergic rhinitis. Eur Respir J. 1998; 11: 1268-73
• 18 Stelmach R, Nunes M, Ribeiro M, Cukier A. Effect of treating allergic rhinitis with corticosteroids in patients with mild-to-moderate persistent asthma. Chest. 2005; 128: 3140-7
• 19 Meltzer EO, Jalowayski AA, Orgel HA, Harris AG. Subjective and objective assessments in patients with seasonal allergic rhinitis: effects of therapy with mometasone furoate nasal spray. J Allergy Clin Immunol. 1998; 102: 39-49
• 20 Meltzer EO, Wenzel S. The efficacy and safety of mometasone furoate delivered via a dry powder inhaler for the treatment of asthma. J Asthma. 2006; 43: 765-72
• 21 Sugimoto Y, Ogawa M, Tai N, Kamei C. Inhibitory effects of glucocorticoids on rat eosinophil superoxide generation and Chemotaxis. Int Immunopharmacol. 2003; 3: 845-52
• 22 Barton BE, Jakway JP, Smith SR, Siegel MI. Cytokine inhibition by a novel steroid, mometasone furoate. Immunopharmacol Immunotoxicol. 1991; 13: 251-61
• 23 Ciprandi G, Tosca MA, Passalacqua G, Canonica GW. Intranasal mometasone furoate reduces late-phase inflammation after allergen challenge. Ann Allergy Asthma Immunol. 2001; 86: 433-8
• 24 Inman MD, Watson RM, Rerecich T, Gauvreau GM, Lutsky BN, Stryszak P et al. Dose-dependent effects of inhaled mometasone furoate on airway function and inflammation after allergen inhalation challenge. Am J Respir Crit Care Med. 2001; 164: 569-74
• 25 Karpel JP, Nayak A, Lumry W, Craig TJ, Kerwin E, Fish JE et al. Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma. Respir Med. 2007; 101: 628-37
• 26 Elwood WJ, Lotvall O, Barnes PJ, Chung KF. Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. J Allergy Clin Immunol. 1991; 88: 951-60
• 27 Schneider T, van Velzen D, Moqbel R, Issekutz AC. Kinetics and quantitation of eosinophil and neutrophil recruitment to allergic lung inflammation in a brown Norway rat model. Am J Respir Cell Mol Biol. 1997; 17: 702-12
• 28 Sugimoto Y, Ishizawa K, Saitou K, Suzuki G, Tarumi T, Nakahara H et al. Effect of mometasone furoate by topical application on allergic rhinitis model in rats. Pharmacology. 2000; 61: 91-5
• 29 Sugimoto Y, Kawamoto E, Chen Z, Kamei C. A new model of allergic rhinitis in rats by topical sensitization and evaluation of H(l)-receptor antagonists. Immunopharmacology. 2000; 48: 1-7
• 30 Vanacker NJ, Palmans E, Pauwels RA, Kips JC. Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats. Eur Respir J. 2002; 20: 873-9
• 31 Vanacker NJ, Palmans E, Pauwels RA, Kips JC. Fluticasone inhibits the progression of allergen-induced structural airway changes. Clin Exp Allergy. 2002; 32: 914-20
• 32 Belvisi MG, Bundschuh DS, Stoeck M, Wicks S, Underwood S, Battram CH et al. Preclinical profile of ciclesonide, a novel corticosteroid for the treatment of asthma. J Pharmacol Exp Ther. 2005; 314: 568-74
• 33 Tsumuro T, Ogawa M, Minami K, Takubo M, Rahman A, Fujii Y et al. Effects of mometasone furoate on a rat allergic rhinitis model. Eur J Pharmacol. 2005; 524: 155-8
• 34 Chapman RW, Sehring SJ, Garlisi CG, Falcone A, Kung TT, Stelts D et al. Anti-inflammatory activity of inhaled mometasone furoate in allergic mice. Arzneimittelforschung. 1998; 48: 384-91
• 35 Wyss D, Bonneau O, Trifilieff A. Synergistic effect of formoterol and mometasone in a mouse model of allergic lung inflammation. Br J Pharmacol. 2007; 152: 83-90
• 36 Celly CS, House A, Sehring SJ, Zhang XY, Jones H, Hey JA et al. Temporal profile of forced expiratory lung function in allergen-challenged Brown-Norway rats. Eur J Pharmacol. 2006; 540: 147-54
• 37 Billah MM, Cooper N, Minnicozzi M, Warneck J, Wang P, Hey JA et al. Pharmacology of N-(3,5-dichloro-l-oxido-4-pyridinyl)-8-methoxy-2(trifluoromethyl)-5-quinoline car-boxamide (SCH 351591), a novel, orally active phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther. 2002; 302: 127-37
• 38 Chapman RW, House A, Jones H, Richard J, Celly C, Prelusky D et al. Effect of inhaled roflumilast on the prevention and resolution of allergen-induced late phase airflow obstruction in Brown Norway rats. Eur J Pharmacol. 2007; 571: 215-21
• 39 Raabe OG, Al-Bayati MA, Teague SV, Rasolt A. Regional deposition of inhaled monodisperse coarse and fine aerosol particles in small laboratory animals. Ann Occup Hyg. 1988; 32: S53-63
• 40 Hsieh T, Yu CP, Oberdörster G. Deposition and clearance models of Ni compounds in the mouse lung and comparisons with the rat models. Aerosol Sci Technol. 1999; 31: 358-72
• 41 Onrust SV, Lamb HM. Mometasone furoate. A review of its intranasal use in allergic rhinitis. Drugs. 1998; 56: 725-45
• 42 McCormack PL, Scott LJ. Fluticasone furoate: intranasal use in allergic rhinitis. Drugs. 2007; 67: 1905-15
• 43 Zitt M, Kosoglou T, Hubbell J. Mometasone furoate nasal spray: a review of safety and systemic effects. Drug Saf. 2007; 30: 317-26
• 44 Braunstahl GJ, Kleinjan A, Overbeek SE, Prins JB, Hoogsteden HC, Fokkens WJ. Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med. 2000; 161: 2051-7
• 45 Gaga M, Lambrou P, Papageorgiou N, Koulouris NG, Kosmas E, Fragakis S et al. Eosinophils are a feature of upper and lower airway pathology in non-atopic asthma, irrespective of the presence of rhinitis. Clin Exp Allergy. 2000; 30: 663-9
• 46 Dahl R. Rhinitis and asthma. Allergic and non-allergic rhinitis. Mygind N, Naclerio RM. Copenhagen; Munksgaard:. 1993; p. 184-8
• 47 Denburg JA, Sehmi R, Saito H, Pil-Seob J, Inman MD, O’Byrne PM. Systemic aspects of allergic disease: bone marrow responses. J Allergy Clin Immunol. 2000; 106 (5 Suppl) S242-6
• 48 Wagner JG, Jiang Q, Harkema JR, Ames BN, Illek B, Roubey RA et al. γ-Tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma. Clin Exp Allergy. 2007; 38: 501-11
• 49 Han DM, Zhou B, Wang T, Wang XD, Fan EZ. Intranasal application of Epstein-Barr virus/lipoplex to abrogate eosinophillia in murine model of allergic rhinitis. Chin Med J (Engl). 2006; 119: 991-7
• 50 Pauluhn J. Overview of inhalation exposure techniques: strengths and weaknesses. Exp Toxicol Pathol. 2005; 57 (Suppl 1:) 111-28
• 51 Noonan M, Karpel JP, Bensch GW, Ramsdell JW, Webb DR, Nolop KB et al. Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler. Ann Allergy Asthma Immunol. 2001; 86: 36-43
• 52 Bernstein DI, Berkowitz RB, Chervinsky P, Dvorin DJ, Finn AF, Gross GN et al. Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler. Respir Med. 1999; 93: 603-12
• 53 Nayak AS, Banov C, Corren J, Feinstein BK, Floreani A, Friedman BF et al. Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma. Ann Allergy Asthma Immunol. 2000; 84: 417-24
• 54 Kemp JP, Berkowitz RB, Miller SD, Murray JJ, Nolop K, Harrison JE. Mometasone furoate administered once daily is as effective as twice-daily administration for treatment of mild-to-moderate persistent asthma. J Allergy Clin Immunol. 2000; 106: 485-92
• 55 Bensch GW, Prenner B, Berkowitz R, Galant S, Ramsdell J, Lutsky B. Once-daily evening administration of mometasone furoate in asthma treatment initiation. Ann Allergy Asthma Immunol. 2006; 96: 533-40
• 56 Holgate ST, Arshad H, Stryszak P, Harrison JE. Mometasone furoate antagonizes AMP-induced bronchoconstriction in patients with mild asthma. J Allergy Clin Immunol. 2000; 105: 906-11
• 57 Magari M, Ikeda M, Asakura M, Kanayama N, Ogawa M, Ohmori H. Suppressive effects of mometasone furoate on an antigen-specific IgE antibody response and production of IL-4 in mice. Immunopharmacol Immunotoxicol. 2006; 28: 491-500