ArticleAntimicrobial agents and chemotherapy2009
The antituberculosis drug pyrazinamide affects the course of cutaneous leishmaniasis in vivo and increases activation of macrophages and dendritic cells.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Differential Regulation of Oxidative Burst by First Line Drugs Used Against Multi Drug-Resistant Tuberculosis in Naïve Human Innate Immune Cells.Antibiotics (Basel, Switzerland) · 2026Article
- Genetic Analysis of Molecular Mechanisms of Drug Resistance inInfection and drug resistance · 2025Review
- Applied Machine Learning Toward Drug Discovery Enhancement: Leishmaniases as a Case Study.Bioinformatics and biology insights · 2022Article
- Nicotinamide Limits Replication of Mycobacterium tuberculosis and Bacille Calmette-Guérin Within Macrophages.The Journal of infectious diseases · 2020Article
- Different macrophage polarization between drug-susceptible and multidrug-resistant pulmonary tuberculosis.BMC infectious diseases · 2020Article
- Pharmacological and Molecular Mechanisms Behind the Sterilizing Activity of Pyrazinamide.Trends in pharmacological sciences · 2019Review
- Impact of the host environment on the antitubercular action of pyrazinamide.EBioMedicine · 2019Review
- Parasitic infections in Malaysian aborigines with pulmonary tuberculosis: a comparative cross-sectional study.Parasitology research · 2019Article
- Article
- Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis.Scientific reports · 2017Article
- Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis.Pharmaceutical research · 2016Article
- Host-Mediated Bioactivation of Pyrazinamide: Implications for Efficacy, Resistance, and Therapeutic Alternatives.ACS infectious diseases · 2015Article
- Ex vivo host and parasite response to antileishmanial drugs and immunomodulators.PLoS neglected tropical diseases · 2015Article
- Apoptosis mediated leishmanicidal activity of Azadirachta indica bioactive fractions is accompanied by Th1 immunostimulatory potential and therapeutic cure in vivo.Parasites & vectors · 2015Article
- Leishmanicidal Activity of Piper nigrum Bioactive Fractions is Interceded via Apoptosis In Vitro and Substantiated by Th1 Immunostimulatory Potential In Vivo.Frontiers in microbiology · 2015Article
- Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.PloS one · 2015Article
- Revisiting Anti-tuberculosis Activity of Pyrazinamide in Mice.Mycobacterial diseases : tuberculosis & leprosy · 2014Article
- Intestinal parasite co-infection among pulmonary tuberculosis cases without human immunodeficiency virus infection in a rural county in China.The American journal of tropical medicine and hygiene · 2014Article
- Article
- Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis.PloS one · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antileishmanial therapy is suboptimal due to toxicity, high cost, and development of resistance to available drugs. Pyrazinamide (PZA) is a constituent of short-course tuberculosis chemotherapy. We investigated the effect of PZA on Leishmania major promastigote and amastigote survival. Promastigotes were more sensitive to the drug than amastigotes, with concentrations at which 50% of parasites were inhibited (MIC(50)) of 16.1 and 8.2 microM, respectively (48 h posttreatment). Moreover, 90% of amastigotes were eliminated at 120 h posttreatment, indicating that longer treatments will result in parasite elimination. Most strikingly, PZA treatment of infected C57BL/6 mice resulted in protection against disease and in a 100-fold reduction in the parasite burden. PZA treatment of J774 cells and bone marrow-derived dendritic cells and macrophages increased interleukin 12, tumor necrosis factor alpha, and activation marker expression, as well as nitric oxide production, suggesting that PZA enhances effective immune responses against the parasite. PZA treatment also activates dendritic cells deficient in Toll-like receptor 2 and 4 expression to initiate a proinflammatory response, confirming that the immunostimulatory effect of PZA is directly caused by the drug and is independent of Toll-like receptor stimulation. These results not only are strongly indicative of the promise of PZA as an alternative antileishmanial chemotherapy but also suggest that PZA causes collateral immunostimulation, a phenomenon that has never been reported for this drug.
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