Administration of pentoxifylline during allergen sensitization dissociates pulmonary allergic inflammation from airway hyperresponsiveness.
Asthma, a chronic inflammatory disease characterized by intermittent, reversible airflow obstruction and airway hyperresponsiveness (AHR), is classically characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1 cytokines (IFN-gamma, IL-12). Recent studies indicating an important role for Th1 immunity in the development of AHR with allergic inflammation suggest that Th1/Th2 balance may be important in determining the association of AHR with allergic inflammation. We hypothesized that administration of pentoxifylline (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production, during allergen (OVA) sensitization and challenge would lead to attenuation of AHR in a murine model of allergic pulmonary inflammation. We found that PTX treatment led to attenuation of AHR when administered at the time of allergen sensitization without affecting other hallmarks of pulmonary allergic inflammation. Attenuation of AHR with PTX treatment was found in the presence of elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and decreased levels of the Th1 cytokine IFN-gamma. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.
Fleming
C M
CM
Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
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Ciota
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Perkins
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Finn
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D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007399:Interphase / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010431:Pentoxifylline / Q000008:administration & dosage*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013909:Thorax
D000336:Aerosols; D000485:Allergens; D016207:Cytokines; D016328:NF-kappa B; D010047:Ovalbumin; D010431:Pentoxifylline