Role of Dexamethasone on immune dysregulation mediated through Th1/Th2 cytokine balance in mice challenged with type 1 diabetes and allergic asthma

Abstract

Dysregulated equilibrium between T helper 1 (Th1) and T helper 2 (Th2) immune responses has been implicated in the pathogenesis of type 1 diabetes (T1D) and asthma. Conflicting evidence exist explaining the association between T1D and asthma and is still a point of debate. In the present study, our objective was to investigate the influence of associated T1Dco morbid condition on the induction of experimental asthma in mice and also to evaluate the efficacy of Dexamethasone (0.5 mg/kg, s.c.ly) in these mice. Type 1 diabetes was induced by a single intravenous injection of alloxan (80 mg/kg) in Balb/c mice. Following diabetes induction, mice were sensitized with an intraperitoneal injection of 50 µg ovalbumin (Ova) emulsified in 2.5 mg aluminum hydroxide on days 3 and 8. From day 13 to day 15, animals were challenged intranasally with 100 µg Ova in 25 µl of sterile saline. Dexamethasone treatment was initiated on sensitization day and continued once in 2 days thereafter until day 15. Control animals received only saline without Ova. On day 16, mice were subjected to nasal hyperresponsiveness (NHR) immediately after the Ova challenge. Bronchioalveolar lavage fluid (BALF), blood, and lungs were collected 1h post completion of NHR for further analysis. Alloxan diabetic mice showed significantly lower levels of eosinophils in BALF and blood with the corresponding decrease in inflammatory cells around airways in hematoxylin & eosin-stained lung sections, but with no change in NHR than in non-diabetics after Ova sensitization and challenge. Dexamethasone treatment showed a significant reduction of airway inflammation and related Th2 immune responses, with a lesser magnitude of efficacy in diabetic asthma mice than in non-diabetic asthma mice. The presence of T1D featured a unique, yet the intermediary stage of asthma induction and also presented an altered magnitude of Dexamethasone efficacy compared to the absence of T1D in the murine model of Ova induced asthma.