Modification of prostanoid secretion in endothelial cells by amphotericin B acting synergistically with interleukin-1beta: possible explanation of proinflammatory effects.
Human umbilical vein endothelial cells were exposed to free-form and lipid-complexed versions of amphotericin B (alone or in combination with human recombinant interleukin [IL]-1 beta) and to culture medium from the human macrophage cell line THP-1 that had been exposed to amphotericin B. Endothelial cells were then incubated with exogenous-labeled arachidonic acid or were stimulated with histamine. Measurement of the resulting prostanoids indicated that amphotericin B and IL-1 beta acted synergistically to increase the ability of endothelial cells to synthesize prostanoids from endogenous and exogenous substrate and to increase expression of cyclooxygenase-2. This resulted in an increase of the ratio of untransformed prostaglandin (PG) H2 to PGI2 released by endothelial cells. Culture medium from amphotericin B-activated macrophages caused similar effects in endothelial cells. The synergistic effect with IL-1 beta was observed with free-form amphotericin B and, to a lesser extent, with lipid-complexed amphotericin B (Abelcet). Differences between Abelcet and the lipisome carrier (AmBisome) were not significantly different with respect to any of the parameters analyzed.
Laboratory of Inflammation Mediators, Centro de Biológica Translacional en Endocrinología, Metabolismo, y Nutrición, Institute of Research of the Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Mercedes
M
Camacho
Esther
E
Gerbolés
Marta
M
Soler
Luís
L
Vila
D000666:Amphotericin B / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D004338:Drug Combinations; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D008081:Liposomes; D008264:Macrophages; D010713:Phosphatidylcholines / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects*
D004338:Drug Combinations; D007375:Interleukin-1; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011453:Prostaglandins; D011994:Recombinant Proteins; C068538:liposomal amphotericin B; D000666:Amphotericin B