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Tumor necrosis factor- alpha synergizes with IFN- gamma in mediating killing of Leishmania major through the induction of nitric oxide.
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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“It is worth noting that IFNγ co-operates with other TH1 cell cytokines and acts synergistically to enhance their ability to eliminate pathogens31,32.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [32]
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Flynn, J., & Chan, J. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.93 · Cited by 1,144
Flynn, J. L., Goldstein, M. M., Chan, J., Triebold, K. J., Pfeffer, K., Lowenstein, C. J., Schrelber, R., Mak, T. W., & Bloom, B. R. (1995) · Immunity · doi:10.1016/1074-7613(95)90001-2 · Cited by 1,678
T-cell quality in memory and protection: implications for vaccine design
Seder, R. A., Darrah, P. A., & Roederer, M. (2008) · Nature reviews. Immunology · doi:10.1038/nri2274 · Cited by 1,565
Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major
Darrah, P. A., Patel, D. T., Luca, P. M. D., Lindsay, R. W. B., Davey, D. F., Flynn, B. J., Hoff, S. T., Andersen, P. L., Reed, S. G., Morris, S. L., et al. (2007) · Nature Medicine · doi:10.1038/nm1592 · Cited by 1,364
The Central Role of CD4+ T Cells in the Antitumor Immune Response
Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D., & Levitsky, H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2357 · Cited by 1,345
Metadata
- 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
- 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
- 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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