Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness

Abstract

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-γ, 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-γ. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.

Investigation of the Antiasthmatic Properties of Ethanol Extract of <i>Callophyllis japonica</i> in Mice

“…Asthma is a chronic respiratory disease characterized by airway hyperresponsiveness (AHR), intermittent pulmonary obstruction, and pulmonary and airway inflammation [1]. The inflammatory response in the asthmatic is associated with the infiltration of mast cells, lymphocytes, and eosinophils into the bronchial lumen and lung tissue.…”

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

“…Readings were averaged over 7 min from the beginning of the nebulization. The whole-body plethysmography system measures changes in box pressure during expiration and inspiration, peak expiratory pressure (PEP), peak inspiratory pressure (PIP), inspiratory time (Ti), expiratory time (Te), and relaxation time (Tr ϭ time of the pressure decay to 36% of total box pressure during expiration) and generates a value called enhanced Pause (Penh) (Penh ϭ PEP/PIP ϫ [{Te Ϫ Tr}/ Tr]), which is associated with airway resistance (10,15,18). We have previously analyzed the identical OVA allergic model with classical measures of lung resistance using tracheostomized and anesthetized mice in Balb/c and C57/BL6 strains (3,4,11,13).…”

“…Mice were sensitized and challenged with allergen ovalbumin (OVA) as previously described (4,(10)(11)(12)(13)(14)(15). Briefly, mice were sensitized by intraperitoneal injection with 10 g chicken OVA and 1 mg Al(OH) 3 (alum) on Days 0 and 7.…”

“…Mice were placed in individual chambers, and 100 mg/ml methacholine was nebulized into the chambers via an inlet for 2 min as previously described (10,(15)(16)(17). Readings were averaged over 7 min from the beginning of the nebulization.…”

“…Each mouse underwent BAL, as previously described (4,(10)(11)(12)(13)(14)(15). Cells were resuspended in RPMI.…”