||Effect of Pentamidine on Cytokine (IL-1Beta, TNFalpha, IL-6) Production by Human Alveolar Macrophages In vitro.
||TRC Environmental Corp., Chapel Hill, NC.;Health Effects Research Lab., Research Triangle Park, NC. Human Studies Div.
Tumor necrosis factor;
In vitro analysis;
Post-translational protein processing;
Polymerase chain reaction;
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||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.
||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
||Reprint: Effect of Pentamidine on Cytokine (IL-1Beta, TNFalpha, IL-6) Production by Human Alveolar Macrophages In vitro.
||57Q; 57B; 57F
||PC A03/MF A01