We compared for the first time the therapeutic potential of a specific
phosphodiesterase 4 (
PDE4) inhibitor,
rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary
allergen exposure of previously sensitized and challenged mice. To address these issues, mice were sensitized and challenged with
ovalbumin (OVA) (primary challenge). Six weeks later, sensitized/challenged mice were reexposed to OVA (secondary challenge) and airway response (resistance [RL] and dynamic compliance [Cdyn]) to inhaled
methacholine was monitored. After secondary OVA challenge, RL significantly increased as did the number of lung inflammatory cells and
IL-4 and
IL-5 production in bronchoalveolar lavage fluid (BALF). Administration of
rolipram, in a dose-dependent manner, significantly prevented both changes in RL and Cdyn, as well as eosinophil, lymphocyte, and neutrophil accumulation in the BALF;
IL-4 and
IL-5 levels in BALF were also significantly reduced. In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eosinophil numbers and
IL-5 production in BALF. Further, goblet cell
hyperplasia was suppressed only by treatment with
rolipram. None of the treatments affected OVA-specific antibody levels. These studies confirm that
IL-5 dependent eosinophilic
inflammation plays an essential role in the development of certain aspects of airway function after rechallenge of sensitized mice and that lymphocytes and neutrophils are also important in the development of altered airway function. The use of agents that inhibit PDE4 may have an important role in the treatment of
asthma in previously sensitized mice.