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.

Pentamidine: An inhibitor of interleukin-1 that acts via a post-translational event / G.J. Rosenthal, E. Corsini, W.A. Craig, C.E. Comment, M.I. Luster. - In: TOXICOLOGY AND APPLIED PHARMACOLOGY. - ISSN 0041-008X. - 107:3(1991), pp. 555-561.

Pentamidine: An inhibitor of interleukin-1 that acts via a post-translational event

E. Corsini
Secondo
;
1991

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.
Settore BIO/14 - Farmacologia
1991
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/181780
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