Recombinant human platelet-activating factor-acetylhydrolase inhibits airway inflammation and hyperreactivity in mouse asthma model

Numerous in vitro and in vivo studies in both animal models and human asthm atics have implicated platelet-activating factor (PAF) as an important infl ammatory mediator in asthma, In a murine asthma model, we examined the anti -inflammatory activities of recombinant human PAF-acetylhydrolase (rPAF-AH) , which converts PAF to biologically inactive lyso-PAF. In this model mice sensitized to OVA by i.p, and intranasal (i.n.) routes are challenged with the allergen by i,n, administration, The OVA challenge elicits an eosinophi l infiltration into the lungs with widespread mucus occlusion of the airway s and results In bronchial hyperreactivity, The administration of rPAF-AH h ad a marked effect on late-phase pulmonary inflammation, which included a s ignificant reduction in airway eosinophil infiltration, mucus hypersecretio n, and airway hyperreactivity in response to methacholine challenge. These studies demonstrate that elevating plasma levels of PAF-AH through the admi nistration of rPAF-AH is effective in blocking the late-phase pulmonary inf lammation that occurs in this murine allergen-challenge asthma model. These results suggest that rPAF-AH may have therapeutic effects in patients with allergic: airway inflammation.