Cited by 522Research on Leishmaniasis StudiesLeprosy Research and TreatmentImmune cells in cancer

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Tumor necrosis factor- alpha synergizes with IFN- gamma in mediating killing of Leishmania major through the induction of nitric oxide.

Liew, F Y, Li, Y, Millott, S·1990·The Journal of Immunology

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Abstract

CBA mice develop cutaneous lesions when infected with Leishmania major. The disease development was significantly reduced by injecting into the lesion a combination of rIFN-gamma and rTNF-alpha. The doses of IFN-gamma and TNF-alpha used were suboptimal in that either cytokine alone did not have any effect. The therapeutic effect of IFN-gamma and TNF-alpha in vivo is reflected in their ability to activate macrophages to kill the intracellular parasites in vitro. The macrophage leishmanicidal activity induced by TNF-alpha and IFN-gamma can be completely inhibited by a specific inhibitor (l-NG monomethyl arginine) of nitric oxide synthesis. There was a direct correlation between the intracellular killing of the parasites and the production of nitric oxide by the macrophages. In contrast, there was no correlation between leishmanicidal activity and superoxide production by macrophages.

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Background
Cloning, characterization and overexpression of two iron superoxide dismutase cDNAs from Leishmania chagasi: role in pathogenesis1Note: L.c.FeSODA and L.c.SODB cDNA sequences have been assigned EMBL/GenBank™ data base accession numbers AF003964 and AF003963, respectively.1,2Note: A previous article on this same topic entitled `Molecular cloning, characterization and expression in Escherichia coli of iron superoxide dismutase cDNA from Leishmania donovani chagasi' by Ismail et al. which was published in Infect Immun 1994;62:657–664 has been retracted.2
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Background
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Background
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Authors: Liew, F. Y., Li, Y., & Millott, S.
Affiliations: Wellcome Trust (GB)
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1990-12
Volume: 145
Issue: 12
Pages: 4306-4310
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.145.12.4306
OpenAlex: W1739247159
Cited by: 522
References: 0
Citations by year: 2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 9 · 2020: 16 · 2019: 7 · 2018: 14 · 2017: 16 · 2016: 11 · 2015: 13 · 2014: 21 · 2013: 16 · 2012: 15
FWCI: 37.31
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: Leishmania major, cutaneous leishmaniasis, TNF-α, interferon-gamma, nitric oxide, macrophage activation, antileishmanial activity, L-NG-monomethylarginine, superoxide, cytokine synergy
MeSH terms: Animals, Arginine, Cytotoxicity, Immunologic, Drug Synergism, Hydrogen Peroxide, Immunity, Cellular, Interferon-gamma, Leishmania tropica, Leishmaniasis, Macrophages, Mice, Inbred CBA, Nitric Oxide, Nitrites, Superoxides, Tumor Necrosis Factor-alpha, omega-N-Methylarginine, Mice

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Tumor necrosis factor- alpha synergizes with IFN- gamma in mediating killing of Leishmania major through the induction of nitric oxide.

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