Plasma Eicosanoid Levels in Tuberculosis and Tuberculosis-Diabetes Co-morbidity Are Associated With Lung Pathology and Bacterial Burden

2019 
Host eicosanoids are lipid mediators of inflammation that are increasingly recognized as important modulators of the host immune response in Mycobacterium tuberculosis infection. Eicosanoids may be crucial for the control of inflammatory responses during active tuberculosis (TB). However, a detailed examination of the association of eicosanoids in TB and TB-diabetes comorbidity (TB-DM) and relationship to disease pathology or bacterial burdens has not been done. To study this, we examined the plasma levels of Lipoxin A4 (LXA4), 15-epi-LXA4, Leukotriene B4 (LTB4) and Prostaglandin E2 (PGE2) in individuals with either TB-DM, TB, diabetes mellitus (DM) or healthy controls (HC). Plasma levels of LXA4, 15-epi-LXA4 and PGE2 were significantly increased while the levels of LTB4 were significantly decreased in TB-DM and TB group compared to DM and HC. The ratio of LXA4 to LTB4 and 15-epiLXA4 to LTB4 was significantly higher in TB-DM compared to TB. Moreover, the levels of LXA4, 15-epi-LXA4 and the ratios of LXA4 to LTB4 and 15-epiLX4 to LTB4 were significantly higher in TB individuals with bilateral or cavitary disease and these markers also exhibited a significant positive relationship with bacterial burden. At the completion of anti-tuberculosis therapy (ATT), levels of LXA4, 15-epi-LXA4 and PGE2 in TB-DM and TB groups were diminished and levels of LTB4 were enhanced in the TB group compared to pre-treatment. Our data suggest that modulation and upregulation of eicosanoids are typical characteristics of TB-DM co-morbidity. Our data also demonstrate that alterations in the eicosanoid levels reflect disease severity and extent in TB and TB-DM and are modulated by ATT
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