Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation.
IL-3 and granulocyte/macrophage colony stimulating factor (GM-CSF) are two cytokines released by activated T lymphocytes that stimulate the growth and differentiation of various hematopoietic cell lines, among which are macrophages. It has been shown that TNF/cachectin, another cytokine that is released mostly by activated macrophages, plays a central role in experimental cerebral malaria (CM), an acute and lethal neurological syndrome induced by Plasmodium berghei ANKA infection in CBA mice. Since CM requires functional CD4+ T lymphocytes to occur, we explored, by injecting rabbit antibodies to murine rIL-3 and/or GM-CSF, whether these cytokines are intermediates in the marked TNF release leading to CM. Treatment of infected mice with each antibody separately had no protective effect. In contrast, when both anti-rGM-CSF and anti-rIL-3 antibodies were injected together; (a) the occurrence of neurological syndrome was prevented in 90% of the cases; (b) the rise in serum TNF was prevented; and (c) macrophage accumulation in the spleen was significantly reduced. Murine CM appears to involve a cytokine cascade in which IL-3 and GM-CSF lead to the accumulation of TNF-releasing macrophages in vivo.
D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D003115:Colony-Stimulating Factors / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000276:immunology*; D007377:Interleukin-3 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008288:Malaria / Q000150:complications*; D051379:Mice; D008808:Mice, Inbred CBA; D010962:Plasmodium berghei; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor