Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs

Departments of 1 Medicine and 2 Pathology, School of Medicine, University of Sao Paulo, São Paulo, Brazil; and 3 Department of Pathology, The University of Vermont, Burlington, Vermont Submitted 2 August 2007 ; accepted in final form 2 April 2008 Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1–5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation. experimental model of chronic allergic pulmonary inflammation; eosinophils; collagen and elastic fibers deposition; lung strip mechanics; tolerization Address for reprint requests and other correspondence: I. F. L. C. Tibério, Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455-Sala 1210, 01246-903, São Paulo SP, Brazil (e-mail: iocalvo{at}uol.com.br )