The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

1658006

Reference Type

Journal Article

Title

The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo

Author(s)

Beshay, E; Croze, F; Prud'homme, GJ

Year

2001

Is Peer Reviewed?

Yes

Journal

Clinical Immunology
ISSN: 1521-6616
EISSN: 1521-7035

Volume

Issue

Page Numbers

272-279

Language

English

PMID

11161985

DOI

10.1006/clim.2000.4964

Web of Science Id

WOS:000166952800016

Abstract

We studied the effects of the phosphodiesterase inhibitors pentoxifylline (PTX) and rolipram (ROL) on nitric oxide (NO) production by macrophages and correlated this with cellular cAMP levels. The RAW 264.7 cell line or mouse peritoneal macrophages were activated with lipopolysaccharide (LPS) and interferon gamma (IFN gamma), with or without ROL, PTX, cAMP analogues, or Forskolin. In vivo, peritoneal macrophages were stimulated with staphylococcal enterotoxin B with or without administration of ROL. Nitrite levels in culture and the total cellular cAMP levels were measured. ROL and PTX suppressed NO production of LPS/IFN gamma-stimulated macrophages. ROL (IC(50) = 68-74 microM) was about 40 times more potent than PTX (IC(50) = 2.4-2.9 mM). The suppression paralleled increased total cellular cAMP level (EC(50) = 68-72 microM) and was mimicked by other cAMP elevating agents. ROL and PTX suppressed inducible NO synthase at the mRNA level. The inhibition of NO production of macrophages by ROL or PTX could be beneficial in NO-mediated inflammatory and/or autoimmune disorders.

Keywords

phosphodiesterase inhibitor; pentoxifylline; rolipram; nitric oxide; macrophage; cytokines; inflammation