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

John C Anthes; Robbie L McLeod; Richard W Chapman; Yanlin Jia; Aileen House; Fernandez Xiomara; Gissela Diaz; Johanna Jimenez; Jennifer Richard; Howard Jones; George Kelly; Michelle Natiello; Aidan Curran; Jonathan E Phillips

doi:10.1055/s-0031-1296359

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2009; 59(1): 13-20
DOI: 10.1055/s-0031-1296359

Antiallergic Agents

Editio Cantor Verlag Aulendorf (Germany)

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

Authors

John C Anthes

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Robbie L McLeod

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Richard W Chapman

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Yanlin Jia

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Aileen House

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Fernandez Xiomara

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Gissela Diaz

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Johanna Jimenez

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Jennifer Richard

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Howard Jones

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
George Kelly

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Michelle Natiello

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Aidan Curran

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)
Jonathan E Phillips

¹Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey (USA)

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

Full Text

References

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