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.
Camacho
Mercedes
M
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.
Gerbolés
Esther
E
Soler
Marta
M
Vila
Luís
L
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