Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.
Anmol RaienSofia DavisMichelle ZhangDavid ZitserMichelle LinGraysen PitcherKrishna BhalodiaSelvakumar SubbianVishwanath VenketaramanPublished in: Cells (2023)
The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis ( M. tb ) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.
Keyphrases
- mycobacterium tuberculosis
- clinical trial
- pulmonary tuberculosis
- lung function
- protein kinase
- oxidative stress
- signaling pathway
- chronic obstructive pulmonary disease
- cystic fibrosis
- open label
- poor prognosis
- human health
- combination therapy
- emergency department
- randomized controlled trial
- body composition
- endoplasmic reticulum stress
- long non coding rna
- tyrosine kinase
- electronic health record
- smoking cessation
- heart rate