Modulation of TNF alpha and IL-6 in a peritonitis model using pentoxifylline

Abstract

Sepsis leads to release of reactants that play an important role in the development of multiple organ failure. The kinetics of two early mediators of the response to sepsis, tumour necrosis factor (TNF alpha) and interleukin 6 (IL-6), and their modulation with pentoxifylline (PTF), were investigated. An established and clinically relevant animal model was employed, and sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. Six hours after the operation, there was an increase in IL-6 in all animals, which declined toward normal by 18 hours. This early phase of IL-6 production was not influenced by PTF. TNF alpha and IL-6 were significantly higher in the CLP group than in the animals treated with PTF at 24 hours. The blood pressure of the CLP group at 24 hours was significantly lower than that of the shams, and this decrease was not influenced by PTF. This decline in blood pressure may have been the stimulus to TNF production and the second phase of IL-6 production, which appeared to be inhibited by PTF. Pentoxifylline appears to attenuate systemic cytokine production in this model and may have a role in the management of clinical sepsis.