Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs

Abstract

Tuberculosis (TB) is a lethal disease and remains one of the top ten causes of mortality by an infectious disease worldwide. It can also result in significant morbidity related to persistent inflammation and tissue damage. Pulmonary TB treatment depends on the prolonged use of multiple drugs ranging from 6 months for drug-susceptible TB to 6-20 months in cases of multi-drug resistant disease, with limited patient tolerance resulting from side effects. Treatment success rates remain low and thus represent a barrier to TB control. Adjunct host-directed therapy (HDT) is an emerging strategy in TB treatment that aims to target the host immune response to Mycobacterium tuberculosis in addition to antimycobacterial drugs. Combined multi-drug treatment with HDT could potentially result in more effective therapies by shortening treatment duration, improving cure success rates and reducing residual tissue damage. This review explores the rationale and challenges to the development and implementation of HDTs through a succinct report of the medications that have completed or are currently being evaluated in ongoing clinical trials.

Keywords: Mycobacterium; adjunct therapy; host-directed therapy; immunotherapies; tuberculosis.

FIGURE 1

Main potential host therapeutic targets (HDT) improve outcome in Mycobacterium tuberculosis. (A) Lipid peroxidation inhibitors, Ibuprofen, Aspirin, N-acetylcysteine, and Vitamin D suppress proinflammatory responses, which decrease inflammation and tissue damage during active stage of the disease. (B) Doxycycline changes the integrity of granuloma and enhances drug accessibility. (C) Vitamin A reduces bacilli growth by apoptosis or auto-phagolysosome. (D) Doxycycline, Statin, and Metformin regulate cell-mediated immune responses, including antigen-specific T cell responses. (E) Some HDT like vitamin D induce autophagy in infected cells.

FIGURE 2

The challenge of finding effective host-directed therapy (HDTs) and the current anti-tuberculosis therapy. Perspectives for clinical studies for HDT efficacy.