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Activation of human macrophages. Comparison of other cytokines with interferon-gamma
Abstract:
Cytokines affecting mononuclear phagocytes were screened for activation of human macrophages to secrete H2O2 and kill toxoplasmas. In contrast to recombinant interferon-gamma (rIFN gamma), the following factors, tested in partially or highly purified form and over a wide range of concentrations, did not augment these functions: native interferon-alpha (nIFN alpha), rIFN alpha A, rIFN alpha D, rIFN beta, colony stimulating factor (type 1) (CSF-1), CSF for granulocytes and macrophages (GM-CSF), pluripotent CSF (p-CSF), tumor necrosis factor (TNF), native interleukin 2 (nIL-2), and rIL-2. Partially purified migration inhibitory factor (MIF) enhanced H2O2-releasing capacity submaximally without inducing antitoxoplasma activity, and warrants further study.
Insights
Recombinant interferon-gamma activates human macrophages to kill toxoplasmas. Other tested cytokines, including various interferons and interleukins, did not significantly enhance this immune response, though migration inhibitory factor showed partial effects.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Human macrophages play a crucial role in innate immunity against pathogens like Toxoplasma gondii.
- Cytokines are key regulators of immune cell function, including macrophage activation.
- Understanding cytokine-mediated macrophage activation is vital for developing novel immunotherapies against parasitic infections.
Purpose of the Study:
- To screen various cytokines for their ability to activate human macrophages.
- To assess the enhancement of hydrogen peroxide (H2O2) secretion and toxocidal activity in macrophages.
- To identify cytokines that can augment macrophage anti-Toxoplasma functions.
Main Methods:
- Screening of multiple cytokines, including interferons, colony-stimulating factors, tumor necrosis factor, and interleukins, on human macrophages.
- Assessment of H2O2 secretion and direct killing of Toxoplasma parasites.
- Testing of cytokines in partially or highly purified forms across a range of concentrations.
Main Results:
- Recombinant interferon-gamma (rIFN gamma) significantly activated macrophages to secrete H2O2 and kill toxoplasmas.
- Native and recombinant forms of interferon-alpha, interferon-beta, colony-stimulating factors (CSF-1, GM-CSF, p-CSF), tumor necrosis factor (TNF), and interleukin-2 (IL-2) did not augment these functions.
- Partially purified migration inhibitory factor (MIF) showed a submaximal enhancement of H2O2 release but did not induce significant anti-Toxoplasma activity.
Conclusions:
- Recombinant interferon-gamma is a potent activator of human macrophages against Toxoplasma gondii.
- Most tested cytokines do not enhance macrophage H2O2 secretion or toxocidal capacity.
- Migration inhibitory factor warrants further investigation for its potential role in macrophage-mediated immunity.