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Cytokine interactions in experimental cutaneous leishmaniasis
W Solbach1, M Röllinghoff, S Stenger
1Institute of Clinical Microbiology, University Erlangen-Nürnberg, Germany.
Behring Institute Mitteilungen
|February 1, 1991
Summary
Interferon-gamma (IFN-gamma) alone activates macrophages to kill Leishmania parasites. Interleukin-4 (IL-4) and Tumor Necrosis Factor-alpha (TNF-alpha) synergize with low IFN-gamma levels for potent antiparasitic activity.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Macrophages are crucial for eliminating intracellular Leishmania major amastigotes.
- Cytokines like IL-4, TNF-alpha, and IFN-gamma play key roles in macrophage activation.
Purpose of the Study:
- To investigate the individual and combined roles of IL-4, TNF-alpha, and IFN-gamma in activating macrophages against Leishmania.
- To elucidate the mechanisms underlying cytokine-mediated macrophage activation.
Main Methods:
- Peritoneal exudate macrophages were cultured with varying concentrations of IL-4, TNF-alpha, and IFN-gamma.
- Macrophage antileishmanial activity was assessed by measuring amastigote elimination.
- The involvement of the L-arginine pathway was tested using NG-monomethyl-L-arginine (L-NMMA).
Main Results:
- IFN-gamma alone induced significant amastigote elimination.
- IL-4 and TNF-alpha alone did not activate macrophages for parasite killing.
- IL-4 and TNF-alpha synergized with sub-optimal IFN-gamma concentrations to enhance antiparasitic activity.
- Endogenous TNF-alpha production was implicated in the IL-4 and IFN-gamma synergy.
- Inhibition of the L-arginine pathway with L-NMMA blocked parasite killing, indicating the role of nitrogen oxides.
Conclusions:
- Macrophage activation against Leishmania is regulated by a complex cytokine network.
- IL-4 and TNF-alpha significantly potentiate the activity of low-dose IFN-gamma.
- The L-arginine-dependent pathway producing nitrogen oxides is essential for parasite killing during synergistic activation.