Tumor necrosis factor-α in combination with interferon-γ, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes

✍ Scribed by Christian Bogdan; Heidrun Moll; Werner Solbach; Martin Röllinghoff

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 476 KB
• Volume: 20
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830200528

✦ Synopsis

Tumor necrosis factor-a in combination with interferon-y , but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes"

We have previously shown that during an infection with Leishmania major, susceptible BALBlc mice, as opposed to mice of a resistant strain (C57BL/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor-a (TNF-a) which is known to be a potent macrophage (MQ,) stimulator in other parasitic diseases. In the present study we investigated whether TNF-a activates MQ for killling of L. major parasites. In the absence of interferon-y (IFN-y) or lipopolysaccharide, TNF-a (0.025-25 000 Ulml) failed to activate peritoneal exudate MQ from BALBlc mice for killling of L. major amastigotes. In the presence of suboptimal doses of IFN-y (5 or 10 U/ml), however, TNF-a mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN-y alone.The combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conclude that the presence of IFN-y is crucial for TNF-a-mediated killing of L. major parasites by MQ. Disease progression in susceptible mice therefore seems to be a consequence of a deficiency of IFN-y and a predominance of TNF-a.