Higher production of tumor necrosis factor alpha in hemozoin-fed—human adherent monocytes is dependent on lipidic component of malarial pigment: new evidences on cytokine regulation in Plasmodium falciparum malaria

To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment. Adherent human monocytes were fed for 3 hours with different meals (native hemozoin; lipid free hemozoin; and control latex particles), then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay. In selected experiments, unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis. Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results. Additionally, hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid, but not by 4-hydroxynonenal. Present data suggest an essential role for lipids in hemozoin-dependent enhanced release of tumor necrosis factor alpha from monocytes, and 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.