Influence of Oral Tolerance on Lung Cytokines Expression and Oxidative Stress Activation in Guinea Pigs with Chronic Inflammation

Abstract

Objective: We had previously demonstrated that oral induced tolerance attenuates lung tissue hyperresponsiveness, eosinophil inflammation and extracellular matrix remodelling in a model of chronic inflammation in guinea pigs. In the present study, we evaluated if these responses were associated to alterations on Th1/Th2 cell expression on airways and distal lung. Methods: 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). After the last inhalation, lungs were removed for the histological analysis using morphometry. We assessed IL-2, IL-4, IL-13, IFN-γ and iNOS both in airways and distal lung. Results: There was an increase in IL-2, IL-4, IL-13, IFN-γ and iNOS positive cells both in airways and alveolar septa in ovalbumin-exposed guinea pigs compared with controls (P<0.05). Both in airways and in lung tissue there was a decrease in IL-4, IL-13 and iNOS positive cells in OT1 and OT2 compared to OVA (P<0.05). Considering IL-2 expression, there was an increase in OT1 and OT2 compared to OVA (P<0.05). We observed positive correlations among the functional responses and some inflammation and oxidative stress pathway activation markers evaluated, especially in alveolar wall. Conclusion: Oral tolerance induces a shift in Th1/Th2 and influences oxidative stress activation both in airways and distal lung of animals with chronic pulmonary allergic inflammation. These results may clarify the mechanisms involved in the attenuation of mechanical responsiveness, inflammation and remodelling of airways and distal lung by oral tolerance, as previously shown in this animal model.