Adaptive immunity involves antigen-specific receptors and requires hours to days for differentiation of effector cells. In contrast, innate immunity involves pattern recognition receptors, and the effector stage occurs within minutes to hours of exposure. Although adaptive antigenic responses are known to play essential roles in allergic asthma, the role of innate immunity is less well characterized.Innate responses involve many cell types and mediators, including surfactant apoproteins (8,9,14,38,40,55). The best known function of surfactant and the surfactant apoproteins is to decrease the surface tension in the alveoli. However, surfactant apoproteins also modulate pulmonary inflammatory responses (8,14,40,55).Two of the surfactant apoproteins, surfactant A (SP-A) and surfactant D (SP-D), are collectins. The collectins are a family of proteins characterized by a collagen-like region and a C-type lectin at their carboxy terminus (20), which also includes mannose-binding protein (18)(19)(20)38). The collectins are important mediators of innate immunity, with their functions including opsonizing bacteria and promoting phagocytosis; mannose-binding protein has also been demonstrated to activate complement (8,20).SP-A and SP-D can modulate innate immune responses in the lung. Both SP-A and SP-D can bind and opsonize bacteria (28,32,48) and fungi (1,9,17,34,37,39,42,44,46,47,54). In addition, SP-A can bind viruses such as influenza A and herpes simplex (35, 49, 50) as well as Pneumocystis carinii (57) and is a chemoattractant for macrophages (56). Mice deficient in SP-A are more susceptible to infections resulting from Pseudomonas (30) and Streptococcus (31) compared with wild-type mice. Moreover, SP-A expression is induced during lung inflammation after exposures that include lipopolysaccharide (LPS), bleomycin, and silica (51).Although allergic pulmonary responses are clearly dependent on adaptive immune responses, the relationship of innate mediators to these responses has not been characterized extensively. Given the potential role of surfactant apoproteins in innate and adaptive in vivo responses, we asked whether the surfactant apoproteins are involved in the pulmonary response to allergen. To investigate pulmonary adaptive responses, we analyzed an in vivo murine model of asthma, elicited by systemic sensitization to the allergen ovalbumin (OVA) followed by aerosolized challenge, resulting in eosinophilic pulmonary infiltrates and airway hyperresponsiveness (AHR; see Refs. 11,26,27,36). We hypothesized that immune responses

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.