TABLE 2.

Immunomodulatory agents as adjunct therapy for tuberculosis treatment.

Name of drug	Intended usage	Adjunct therapeutic effect against TB	Quality of evidence
Metformin	Treatment of type-2 diabetes	Restricts the growth of mycobacteria through the induction of mitochondrial production of reactive oxygen species (Singhal et al., 2014).	Low: due to confounding in observational data, variable dosing, and inconsistent populations.
Loperamide	Diarrheal treatment	It increases the ability of macrophages to clear Mtb by stimulating the reduction of TNFα, which also reduces tissue damage (Juárez et al., 2018).	Very low: due to lack of human trials; limited to macrophage assays with no clinical relevance to TB patients.
Statins	Treatment of cardiovascular and hyperlipidemic diseases	Statins are known to prevent the uptake of Mtb into host cells which is essential for Mtb survival by inhibiting phagocytosis (Fatima et al., 2021).	Low: confounding (e.g., cardiovascular comorbidities); focus on phagocytosis inhibition without randomized control trials (RCTs).
NSAIDs	Anti-inflammatory agents	Mitigates the inflammation resulting from the influx of monocytes, lymphocytes, and neutrophils (Fatima et al., 2021).	Low: due to inconsistent inflammation outcomes; scanty TB-specific human data.
Salazosulfapyridine	Management of rheumatoid arthritis	It stimulates the Mtb clearance of macrophages by inducing the activation of NADPH oxidase which leads to the oxidation of mycothiol within Mtb-infected macrophages, rather than through the production of the metabolite 5-aminosalicylic acid (Mi et al., 2024).	Very low: due to lack of clinical trials; purely in vitro mechanistic exploration.
Verapamil	Treatment of cardiovascular diseases and high blood pressure	It disrupts the membrane function of Mtb and induces a membrane stress response. Also, it increases the efficacy of standard anti-TB drugs (Chen et al., 2018).	Low: due to lack of human trials; limited to membrane disruption assays.
Chicoric acid	Treatment of liver disorders	Enhances the cell surface expression of HLA-DR and CD14 molecules on macrophages and increases the production of nitric oxide in macrophages thus preventing the growth of Mtb within macrophages (Abd-Nikfarjam et al., 2018).	Very Low: no clinical or animal validation.
Corticosteroids	Treatment of inflammatory disorders	Reduces inflammation in TB patients with complications like TB meningitis and pericarditis by modulating inflammatory mediator function, suppressing the humoral immune response, and inhibiting leucocyte infiltration to the site of infection (Young et al., 2020).	Moderate: benefits confined to severe inflammation (e.g., pericarditis); small trial sizes.
TNF-α Inhibitors	Anti-inflammatory agents and immunosuppressants.	Increase Mtb susceptibility and exposure to the standard anti-TB drugs by disrupting and penetrating granulomas to expose Mtb bacilli to the anti-TB drugs (Young et al., 2020).	Moderate: increased TB reactivation risk in immunocompromised patients; not tested as direct TB adjuncts.
Vitamin D	Management of autoimmune diseases like multiple sclerosis and rheumatoid arthritis	Stimulates the production of antimicrobial peptides (cathelicidin and defensins), that directly kill Mtb by disrupting the bacterial membranes and enhancing phagolysosome formation in macrophages (Papagni et al., 2022).	Low to moderate: variable antimicrobial peptide effects; small, diverse cohorts.