PENTOXIFYLLINE DECREASES BODY-WEIGHT LOSS AND MUSCLE PROTEIN WASTING CHARACTERISTICS OF SEPSIS

Sepsis induces metabolic disorders that include loss of body weight, m uscle wasting, and acute-phase protein synthesis in liver. Cytokines a re generally recognized as active mediators of these disorders, and th e implication of tumor necrosis factor (TNF) has been frequently discu ssed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve o ur understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolis m in the following three groups of rats: infected control rats (INF-C) ; infected rats pretreated with pentoxifylline (PTX-INF), which is a p otent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF gr oup pretreated with pentoxifylline. Pentoxifylline nearly completely s uppressed TNF secretion but did not influence the transient fall in re ctal temperature, the decreased hematocrit, and the increased liver pr otein mass and synthesis observed in INF-C rats. Pentoxifylline decrea sed the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle prote in synthesis induced by infection. The overall data indicate that pent oxifylline is an effective agent in mitigating the characteristic musc le protein wasting induced by sepsis and confirm the limited role of T NF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein bal ance in muscle but do not allow discarding possible implication of oth er mediators that would be inhibited by pentoxifylline.