New pharmacological studies with pentoxifylline

Issue title: Proceedings of the Seventh International Congress of Biorheology. Part I. Palais des Congrès, Nancy, France, 18–23 June 1989. Dedicated to Richard Skalak

Guest editors: Alfred L. Copley and Jean-François Stoltz

Article type: Research Article

Authors: Novick Jr., William J.^a | Sullivan, Gail^b | Mandell, Gerald^b

Affiliations: [a] Hoechst-Roussel Pharmaceuticals Inc., Somerville, NJ, USA | [b] University of Virginia, Charlottesville, VA, USA

Note: [] Accepted by: Editor G.W. Schmid-Schönbein

Abstract: Polymorphonuclear (PMN) overactivation plays a critical role in microcirculation as well as in conditions such as multiorgan failure (MOF). Pentoxifylline has been shown to prevent PMN activation by endotoxin and cytokines such as TNFalpha and IL-1. In addition, MOF induced by IL-2 in animals can be prevented by pentoxifylline. The present studies evaluated two aspects of PMN activation and pentoxifylline interaction. The first was the time sequence for pentoxifylline prevention of TNFalpha activation and the second was the activity of pentoxifylline on amphotericin B activation of PMNs. TNFalpha activation of PMNs is blocked by pentoxifylline when cells are exposed to pentoxifylline prior to TNFalpha or after TNFalpha. Amphotericin B activation of PMNs was demonstrated by a decreased chemotaxis, increased chemiluminescence, and increased PMN spreading. In all conditions, pentoxifylline decreased amphotericin B activation of PMNs. These results suggest that pentoxifylline can reverse cytokine activation of PMNs and that pentoxifylline may alter some of the toxic effects of amphotericin.

Keywords: Polymorphonuclear leukocytes, tissue necrosis factor (TNF), multiorgan failure (MOF)

DOI: 10.3233/BIR-1990-273-422

Journal: Biorheology, vol. 27, no. 3-4, pp. 449-454, 1990