INHIBITION OF TUMOR-NECROSIS-FACTOR PRODUCTION AND ICAM-1 EXPRESSION BY PENTOXIFYLLINE - BENEFICIAL-EFFECTS IN SEPSIS SYNDROME

Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and septic shock. Suppression of its biosynthesis might therefo re be one of the strategies in the treatment of sepsis. When periphera l white blood cells were stimulated with either E, coEi lipopolysaccha ride (LPS) or Staphylococcus aureus, pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate inhibitory effect was observ ed on the induction of interleukin 6 (IL-6). PTX inhibited not only th e TNF production of monocytes, but also the TNF secretion of both gran ulocytes and unseparated whole blood. The in vitro TNF and IL-6 produc ing capacities were higher in septic patients (n = 31) than in healthy blood donors (n = 15). Administration of PTX (400 mg/day) to 20 of th e septic patients resulted in TNF production similar to that found in healthy controls. It also subsequently led to an improvement of the cl inical status classified by the APACHE II score. The soluble intercell ular adhesion molecule-1 (sICAM-1) level was significantly higher in t he sera of septic patients before PTX treatment (800-1200 ng/ml) than in normal individuals (50-150 ng/ml), but it decreased following PTX t herapy. Cytofluorometric analysis revealed that the expression of ICAM -1 on stimulated mononuclear cells was inhibited by PTX. It is presume d that the suppressive effect of pentoxifylline on TNF production may be of clinical importance, improving the therapeutic strategies in sep tic syndrome.