A Th2 response to chronic intermittent antigen exposure induces pulmonary vascular muscularization (96.8)

Abstract

Abstract Pulmonary arterial hypertension is associated with pulmonary vascular remodeling (PVRm) and its incidence is increased in many autoimmune diseases and chronic inflammatory lung diseases. Currently it is not known whether inflammatory and immune responses are cause or consequence of PVRm. In this study immunized mice were intermittently exposed to inhaled soluble antigen over a period of several weeks. The antigen exposure induced dramatic PVRm in a CD4 T cell dependent manner. PVRm was characterized by hyperplasia of smooth muscle cells. To identify pathogenic mediators, IL-4 deficient mice and wild type mice transiently given an IL-13 blocker were examined. In both cases, the mice developed significantly less PVRm relative to immunized, antigen challenged, control wild type mice. Mice given recombinant IL-13 intranasally did not develop severe vascular muscularization indicating that IL-13 and, most likely IL-4 promote PVRm indirectly. In conclusion, our data are the first to provide proof of concept that the adaptive immune response to inhaled antigen can cause PVRm. Supported by: Flight Attendant Medical Research Institute, Stony Wold Herbert Fund, American Lung Association of the City of New York