INHIBITORY EFFECTS OF PENTOXIFYLLINE ON LPS-INDUCED LEUKOCYTE ADHESION AND MACROMOLECULAR EXTRAVASATION IN THE MICROCIRCULATION

Pentoxifylline (PTX) has been shown to combat effectively induced endo toxin symptoms of shock or inflammation by reducing both leukocyte act ivation and endogenous cytokine formation. With regard to blood perfus ion, inflammation is defined as a local reaction to injury of the livi ng microvasculature and its content. Leukocyte margination, rolling, a dhesion, and emigration is mediated by adhesion molecules along the en dothelium of postcapillary venules and is considered to be an importan t step in the inflammatory response. Changes in the vascular integrity can be estimated in terms of increased extravasation of macromolecule s. Using intravital microscopy with the help of an analogous video ima ge processing system we measured the effect of PTX on lipopolysacchari de (LPS, 15 mg/kg i.v.) induced leukocyte adhesion and extravasation o f FITC-rat serum albumin (FITC-RSA) in rat mesenteric venules. The cha nges in vascular permeability correlates significantly (r = 0.75) with a locally increased number of adherent leukocytes. PTX significantly inhibits both leukocyte adhesion and extravasation of FITC-RSA dose de pendently. Our results indicate that PTX effectively preserves vascula r integrity in the microcirculation by acting primarily on LPS-induced leukocyte adhesion.