N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis

• DOI: 10.1016/j.jinf.2024.106379
• Publication Date: 2025-01-05T00:18:27Z
• Authors: Daniel Adon Mapamba; Issa Sabi; Julieth Lalashowi; Elingarami Sauli; Joram Buza; Willyhelmina Olomi; Bariki Mtafya; Michael Kibona; Abhishek Bakuli; Andrea Rachow; Kavindhran Velen; Michael Hoelscher; Nyanda E. Ntinginya; Salome Charalambous; Gavin Churchyard; Robert S. Wallis
• Keywords: Adjunctive treatment; Ex vivo

<h2>Abstract</h2><h3>Background</h3> Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed reduce this burden. N-acetylcysteine (NAC) provides conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes a trial adjunctive NAC in patients with pulmonary tuberculosis, finding that improved secondary endpoint recovery function. Here we report effects on biomarkers oxidation, inflammation, and infection trial. <h3>Methods</h3> 140 adults moderate or far-advanced were randomly assigned standard treatment without 1200mg twice daily months 1-4. Sputum blood samples obtained at specified intervals measure total MTB-induced cytokines, haemoglobin, whole mycobactericidal activity (WBA), sputum MTB <h3>Results</h3> rapidly increased glutathione (P<.0001), but levels did not reach those healthy volunteers (P<.001). reduced TNF-α (P =.011) affecting IL-10, accelerated hemoglobin participants low values entry. affect killing <i>ex vivo</i> culture slow clearance from (P=0.003). <h3>Conclusion</h3> Adjunctive showed anti-inflammatory consistent amelioration immunopathology seen preclinical models. Two antimicrobial discordant results; neither demonstrated enhanced preclinically. The reduction oxidative stress inflammation by may explain its function post-TB.