Diabetes Downregulates Allergen-Induced Airway Inflammation in Mice

Abstract

Previous studies described that allergic diseases, including asthma, occur less often than expected in patients with type 1 diabetes. Here, we investigated the influence of diabetes on allergic airway inflammation in a model of experimental asthma in mice. Diabetes was induced by intravenous injection of alloxan into 12 h-fasted A/J mice, followed by subcutaneous sensitization with ovalbumin (OVA) and aluminum hydroxide (Al(OH)3), on days 5 and 19 after diabetes induction. Animals were intranasally challenged with OVA (25 μg), from day 24 to day 26. Alloxan-induced diabetes significantly attenuated airway inflammation as attested by the lower number of total leukocytes in the bronchoalveolar lavage fluid, mainly neutrophils and eosinophils. Suppression of eosinophil infiltration in the peribronchiolar space and generation of eosinophilotactic mediators, such as CCL-11/eotaxin, CCL-3/MIP-1α, and IL-5, were noted in the lungs of diabetic sensitized mice. In parallel, reduction of airway hyperreactivity (AHR) to methacholine, mucus production, and serum IgE levels was also noted under diabetic conditions. Our findings show that alloxan diabetes caused attenuation of lung allergic inflammatory response in A/J mice, by a mechanism possibly associated with downregulation of IgE antibody production.

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

“…However, the severity of airway in lammation in lung sections and Th2-mediated eosinophilic response were diminished in alloxan diabetic mice compared to non-diabetic mice after the Ova challenge. (Carvalho et al, 2018), reported similar indings in alloxan diabetic A/J mice after Ova sensitization and challenge. These results were also correlated with decreased secretions of Th2 responsive IL-4 in both BALF and serum of diabetic asthma mice compared to non-diabetic asthma mice.…”

“…Our results are in line with the observations seen in diabetic animals and could be possibly explained by the decrease in mast cell degranulation and mast cell numbers in these animals (Cavalher-Machado, 2004;Carvalho et al, 2005). It is notable that diabetic animals present decreased in lammatory cellular in iltration in lung airway spaces after allergen challenge (Carvalho et al, 2018;Kolahian et al, 2011).…”

“…Diabetic and non-diabetic mice were sensitized on day 3, and 8 with an intraperitoneal (i.p) injection of 50 µg ovalbumin (Ova) emulsi ied in 2.5 mg aluminum hydroxide (Al(OH) 3 )to a total volume of 0.2 ml in PBS, followed by intranasal challenge with 100 µg Ova/25 µl of sterile saline (4% w/v Ova) on days 13, 14 and 15 as described previously with modi ications (Carvalho et al, 2018;Fernandez-Rodriguez et al, 2008). Control mice received only sterile saline without Ova.…”

“…In addition, diabetes-prone autoimmune NOD mice demonstrated exacerbated asthma symptoms compared to normal Balb/c mice indicating a positive association of T1D and asthma (Araujo et al, 2004). However, a recent study in diabetic A/J mice induced by alloxan con irmed the down-regulation of allergic in lammation in the lungs (Carvalho et al, 2018).…”

Insulin Modulates the Immune Cell Phenotype in Pulmonary Allergic Inflammation and Increases Pulmonary Resistance in Diabetic Mice

“…Eosinophils release proteins that can damage the epithelial barrier, causing enzymatic degradation of mediators or impairing the bronchoprotective effect (14)(15)(16). Clinical (17,18) and experimental data (19,20) suggest that the immune response is impaired in type 1 diabetic individuals. Several aspects of this association have already been described: the onset of diabetes mellitus type 1 (DM1) in patients who have previously been diagnosed with asthma improves the asthmatic condition, but the treatment of diabetic patients with insulin, which is commonly used to treat DM1, aggravates asthma (21,22).…”