Effect of BEA on the expression of 11-βHSD1 and 11-βHSD2, corticosterone and cortisone in the lungs and liver.
In the lung, treatment with BEA in TB and T2D-TB groups induced significant lower expression of 11-βHSD1 after one and two months of treatment when compared with the control group (Fig. 5). This effect was even more evident in the liver of T2D-TB group, which also showed complete disappearance of steatosis and hyperglycemia (Fig. 6D).
The effects of BEA on 11-βHSD1 gene expression in the infected lung were in concordance with the corticosterone immunehistochemistry staining, and its quantitative evaluation by digital pathology (Fig. 5A). BEA significantly decreased active corticosterone in TB and TB/T2D mice, being more pronounced in the TB group (Fig. 5C). In contrast, the expression of 11-βHSD2 after one and two months of BEA treatment showed a significant increase in the TB group, and cortisone was increased in both groups (Fig. 5D, and 5E).
Thus, it seems that BEA is a regulator of the genetic expression of these enzymes in the lung and liver, inducing lower expression of 11-βHSD1 and higher gene expression of 11-βHSD2. In consequence BEA induced lower production of active corticosterone and higher production of inactive cortisone, which could contribute to increase the expression of the pro-inflammatory cytokines TNF-α and IFN-γ decreasing the pulmonary bacillary loads. In the liver BEA improved lipid and glucose metabolism and normalized liver histology and glucose blood concentrations.
Thus, BEA improved the immune response and metabolism of the comorbidity T2D/TB, suggesting that it could be a potential new immune therapeutic agent with beneficial immune, endocrine and metabolic activities.