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RECORD NUMBER: 2 OF 9

Main Title Effect of Pentamidine on Cytokine (IL-1Beta, TNFalpha, IL-6) Production by Human Alveolar Macrophages In vitro.
Author Quay, J.; Rosenthal, G.; Becker, S.;
CORP Author TRC Environmental Corp., Chapel Hill, NC.;Health Effects Research Lab., Research Triangle Park, NC. Human Studies Div.
Publisher cJul 93
Year Published 1993
Report Number EPA-68-D0-0110; EPA/600/J-94/540;
Stock Number PB95-148029
Subjects Pentamidine; Pharmacology; Interleukin-1; Tumor necrosis factor; Interleukin-6; Alveolar macrophages; Glyceraldehydephosphate dehydrogenase; Biosynthesis; In vitro analysis; Cell survival; Lipopolysaccharides; Post-translational protein processing; Genetic transcription; Northern blotting; Polymerase chain reaction; Messenger RNA; Ornithine decarboxylase; Kinetics; Reprints;
Holdings
Library   Call Number Additional Info Location Date Modified
NTIS PB95-148029 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 03/06/1995
Collation 16p
Abstract Pentamidine (Pe) is an aromatic diamidine drug used clinically to treat Pneumocystis carinii pneumonia by aerosol inhalation. Nothing has been reported about the effects of this drug on human alveolar macrophage (AM) properties. In the study AM were exposed in vitro to various concentrations of Pe along or in combination with bacterial endotoxin (LPS). Super-natants were collected at 3, 6, and 24 h and assayed for secreted IL-1beta, IL-6, and TNFalpha. While the drug did not induce release of these cytokines, LPS-induced secretion of all three cytokines was inhibited by Pe in a dose-dependent manner. Reduced steady-state mRNA levels were found as early as 3 h after LPS stimulation, with Pe concentrations corresponding to those that decreased cytokine secretion. At the later time points, Pe also inhibited beta-actin, ornithine decarboxylase, and GAPDH mRNA expression, indicating that pentamidine had a general toxic effect on mRNA transcription in the macrophages. It is concluded that Pe, at pharmaceutically relevant concentrations and with apparent low cytotoxicity as determined by dye uptake, nonspecifically inhibits cytokine production by a toxic effect on transcriptional events.
Supplementary Notes Pub. in Experimental Lung Research, v19 n4 p429-443 Jul 93. Sponsored by Health Effects Research Lab., Research Triangle Park, NC. Human Studies Div.
NTIS Title Notes Journal article.
Title Annotations Reprint: Effect of Pentamidine on Cytokine (IL-1Beta, TNFalpha, IL-6) Production by Human Alveolar Macrophages In vitro.
Category Codes 57Q; 57B; 57F
NTIS Prices PC A03/MF A01
Primary Description 600/10
Document Type NT
Control Number 503414646
Cataloging Source NTIS/MT
Origin NTIS
Type CAT


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