Higher production of tumor necrosis factor alpha inhemozoin-fed human adherent monocytes is dependent onlipidic component of malarial pigment: new evidences on cytokine regulation in P. falciparum malaria

Objective: To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment. Methods: 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. Results: 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. Conclusions: 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.