Inhibition of tumor necrosis factor production and ICAM-1 expression by pentoxifylline: beneficial effects in sepsis syndrome
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Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and septic shock. Suppression of its biosynthesis might therefore be one of the strategies in the treatment of sepsis. When peripheral white blood cells were stimulated with eitherE. coli lipopolysaccharide (LPS) orStaphylococcus aureus, pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate inhibitory effect was observed on the induction of interleukin 6 (IL-6). PTX inhibited not only the TNF production of monocytes, but also the TNF and IL-6 producing capacities were higher in septic patients (n=31) than in healthy blood donors (n=15). Administration of PTX (400 mg/day) to 20 of the septic patients resulted in TNF production similar to that found in healthy controls. It also subsequently led to an improvement of the clinical status classified by the APACHE II score. The soluble intercellula adhesion molecule-1 (sICAM-1) level was significantly higher in the sera of septic patients before PTX treatment (800–1200 ng/ml) than in normal individuals (50–150 ng/ml), but it decreased following PTX therapy. Cytofluorometric analysis revealed that the expression of ICAM-1 on stimulated mononuclear cells was inhibited by PTX. It is presumed that the suppressive effect of pentoxifylline on TNF production may be of clinical importance, improving the therapeutic strategies in septic syndrome.
Key wordsPentoxifylline Sepsis TNF IL-6 ICAM-1
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