title: Pentamidine: an inhibitor of interleukin-1 that acts via a post-translational event.
abstract: Pharmacologic inhibition of cytokines, particularly interleukin-1 (IL-1), potentially has numerous therapeutic applications in inflammatory diseases. We demonstrate that pentamidine, an aromatic diamidine currently used to treat Pneumocystis carinii pneumonia, is a specific and effective inhibitor of cellular IL-1 release from macrophages, and we have shown that this blockage occurs at neither the transcriptional nor the translational level. Pentamidine induced inhibition of IL-1 occurs via an alteration in the post-translational modification of the protein, altering the intracellular and/or membrane cleavage of the 31-kDa pro-IL-1 to the 17-kDa secreted form. In addition, pentamidine exhibited less broad immunosuppressive actions when compared to a corticosteroid, the classical therapeutics utilized for inhibition of cytokine production.
authors.affiliation: National Institute of Environmental Health Sciences, Division of Toxicology Research and Testing Research Triangle Park, North Carolina 27709.
authors.forename: G J
authors.initials: GJ
authors.lastname: Rosenthal
authors.forename: E
authors.initials: E
authors.lastname: Corsini
authors.forename: W A
authors.initials: WA
authors.lastname: Craig
authors.forename: C E
authors.initials: CE
authors.lastname: Comment
authors.forename: M I
authors.initials: MI
authors.lastname: Luster
mesh_terms: D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010419:Pentamidine / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D010419:Pentamidine