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Journal of Pharmacology and Experimental Therapeutics

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OtherPULMONARY PHARMACOLOGY

Fluticasone Propionate and Pentamidine Isethionate Reduce Airway Hyperreactivity, Pulmonary Eosinophilia and Pulmonary Dendritic Cell Response in a Guinea Pig Model of Asthma

Tracey E. Lawrence, Lyndell L. Millecchia and Jeffrey S. Fedan
Journal of Pharmacology and Experimental Therapeutics January 1998, 284 (1) 222-227;
Tracey E. Lawrence
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Lyndell L. Millecchia
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Jeffrey S. Fedan
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Abstract

In this study, we examined the effects of fluticasone propionate (FP) and pentamidine isethionate (PI) on antigen-induced lung inflammation and airway hyperreactivity in guinea pigs. Male guinea pigs were sensitized on days 0 and 14 with 10 μg of ovalbumin (OVA) plus 1 mg of Al(OH)3. On day 21, animals were challenged with a 2% OVA aerosol inhalation until they developed pulmonary obstruction. Animals were treated with aerosol inhalation of FP (2 ml of 0.5 mg/ml, five consecutive doses at 12-hr intervals with the last dose given 6 hr before OVA challenge) or PI (30 mg/ml for 30 min 1 hr before OVA challenge), and control animals received no drug before OVA challenge. Airway reactivity to methacholine (MCh) was assessed before sensitization and 18 hr after OVA challenge. At 18 hr after challenge, histological sections of trachea and lung were examined for eosinophil, dendritic cell (DC) and macrophage cell densities in the airways. In control animals, OVA evoked airway hyperreactivity to MCh in conjunction with pulmonary eosinophilia and increases in DC prevalence in the trachea and bronchi. Treatment with FP or PI abolished the OVA-induced hyperresponsiveness and significantly reduced the OVA-induced increases in eosinophils and DCs in the airways. FP and PI had no effect on saline-treated animals. Our study indicates that both inhaled FP and inhaled PI reduce antigen-induced airway hyperreactivity and pulmonary inflammation in guinea pigs. The results also suggest that the DC is a target of the anti-inflammatory effects of these drugs in the airways.

Footnotes

  • Send reprint requests to: Dr. Jeffrey S. Fedan, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505. E-mail: jsf2{at}cdc.gov.

  • ↵1 This work was supported in part by National Institutes of Health Grant 5-T32-GM07039 and Berlex Biosciences.

  • Abbreviations:
    BF
    breathing frequency
    DAB
    diaminobenzidine
    DC
    dendritic cells
    FP
    fluticasone propionate
    OVA
    ovalbumin
    PI
    pentamidine isethionate
    MCh
    methacholine
    SRaw
    specific airway resistance
    • Received May 19, 1997.
    • Accepted September 26, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 1
1 Jan 1998
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OtherPULMONARY PHARMACOLOGY

Fluticasone Propionate and Pentamidine Isethionate Reduce Airway Hyperreactivity, Pulmonary Eosinophilia and Pulmonary Dendritic Cell Response in a Guinea Pig Model of Asthma

Tracey E. Lawrence, Lyndell L. Millecchia and Jeffrey S. Fedan
Journal of Pharmacology and Experimental Therapeutics January 1, 1998, 284 (1) 222-227;

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OtherPULMONARY PHARMACOLOGY

Fluticasone Propionate and Pentamidine Isethionate Reduce Airway Hyperreactivity, Pulmonary Eosinophilia and Pulmonary Dendritic Cell Response in a Guinea Pig Model of Asthma

Tracey E. Lawrence, Lyndell L. Millecchia and Jeffrey S. Fedan
Journal of Pharmacology and Experimental Therapeutics January 1, 1998, 284 (1) 222-227;
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