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EFFECT OF PENTAMIDINE ON CYTOKINE (IL-1B, TNFA, IL-6) PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES IN VITRO
Citation:
Quay, J., G. Rosenthal, AND S. Becker. EFFECT OF PENTAMIDINE ON CYTOKINE (IL-1B, TNFA, IL-6) PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES IN VITRO. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/540.
Description:
Pentamidine (Pe) is an aromatic diamidine drug used clinically to treat Pneumocystis carinii pneumonia by aerosol inhalation. othing has been reported about the effects of this drug on human alveolar macrophage (AM) properties. n this study AM were exposed in vitro to various concentrations of Pe (10-4 M - 10-6 M) alone or in combination with bacterial endotoxin (LPS). upernatants were collected at 3,6, and 24 hours and assayed for secreted IL-1B, IL-6, and TNFa. hile 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. t the most effective Pe dose, 10-5 M, AM viability as determined by trypan blue dye exclusion, was reduced by 14% at 24 hours, while no effect on viability was seen at lower concentrations. RNA expression of all three cytokines was examined by PCR and Northern analysis to establish if the decrease in cytokine secretion was determined on a pre or post-translational level. educed steady state mRNA levels were found as early as 3 hours after LPS stimulation with Pe concentrations corresponding to those which decreased cytokine secretion. t the later timepoints, Pe also inhibited B-actin, ornithine decarboxylase, and GAPDH mRNA expression indicating that pentamidine had a general toxic effect on MRNA transcription in the macrophages. hus, we conclude that Pe, at pharmaceutically relevant