Abstract
Host eicosanoids are lipid mediators of inflammation that are commonly accepted as important modulators of the host immune response in Mycobacterium tuberculosis infection. During active tuberculosis (TB), eicosanoids may play an important role in the regulation of inflammatory responses. However, a detailed investigation of the relationship of eicosanoids in TB and TB-diabetes comorbidity (TB-DM) and association to disease pathology or bacterial burdens has not been studied. 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 enhanced 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 increased in TB individuals with bilateral or cavitary disease and these markers also revealed 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 imply that alteration and upregulation of eicosanoids are standard characteristics of TB-DM co-morbidity. Our data also demonstrate that modulation in the eicosanoid levels reflect disease severity and extent in TB and TB-DM and are modulated by ATT.
Highlights
Tuberculosis (TB) and diabetes mellitus (DM) are two of the most common diseases worldwide and often occur in the same geographical regions (Dooley and Chaisson, 2009)
Lipoxin A4 (LXA4), Leukotriene B4 (LTB4), and Prostaglandin E2 (PGE2) have been described to be associated with pro-inflammatory cytokine modulation in TB, we examined the association between the plasma levels of eicosanoids in all TB individuals with pro-inflammatory cytokines (Figure 6)
The interplay among the eicosanoids, PGE2 and LXA4 is known to affect the type of cell death in infected macrophages
Summary
Tuberculosis (TB) and diabetes mellitus (DM) are two of the most common diseases worldwide and often occur in the same geographical regions (Dooley and Chaisson, 2009) The occurrence of this co-morbidity poses a major threat to the global program for elimination of tuberculosis (Lonnroth et al, 2015). The enzyme 5-lipoxygenase is essential for the generation of lipoxin and leukotriene mediators from arachidonic acid, while the enzymes cyclooxygenase−1 and 2 are required for the generation of prostaglandins (Das, 2017). These lipid mediators have been shown to exert major influence on the outcomes of experimental M. tuberculosis (M. tb) infection (Mayer-Barber and Sher, 2015). The role in eicosanoids in human TB and TB-DM co-morbidity has been poorly explored
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
