Release of TNF-alpha and IL-1beta from porcine brain endothelium corresponds to the pyrogenic potential of three marketed formulations of amphotericin.
BACKGROUND
Formulations of amphotericin include a deoxycholate suspension (d-Amph), an amphotericin-B lipid complex (Ablc), and a liposomal product (L-Amph). Fever is most frequent with d-Amph, intermediate with Ablc, and lowest with L-Amph.


OBJECTIVE
To determine if the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1) from brain endothelium corresponds to the incidence of amphotericin fever.


RESULTS
Release of TNF-alpha and IL-1beta after L-Amph treatment was similar to negative controls while after d-Amph treatment release was similar to lipopolysaccharide. Ablc treatment produced intermediate pyrogen release.NF-kappaB expression, a transcriptional regulator for TNF-alpha and IL-1beta genes, corresponded to this secretion pattern. TNF-alpha release was elevated 2 hours (p = 0.0021) after treatment while significant elevations in IL-1beta required 6 hours (p = 0.0009).


CONCLUSIONS
Results from this in vitro study suggest that amphotericin fever may be directly mediated by brain endothelium. These experiments also suggest that amphotericin fever is initially mediated by TNF-alpha.
McGuire
T R
TR
Department of Pharmacy Practice, University of Nebraska College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA. trmcguir@unmc.edu
Trickler
W J
WJ
Smith
L
L
Hoie
E B
EB
Miller
D W
DW
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003840:Deoxycholic Acid; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005334:Fever / Q000139:chemically induced*; D007375:Interleukin-1 / Q000378:metabolism*; D008055:Lipids; D008081:Liposomes; D016328:NF-kappa B / Q000378:metabolism; D011749:Pyrogens / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013535:Suspensions; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008055:Lipids; D008081:Liposomes; D016328:NF-kappa B; D011749:Pyrogens; D013535:Suspensions; D014409:Tumor Necrosis Factor-alpha; D003840:Deoxycholic Acid; D000666:Amphotericin B