Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Abstract

Tumor necrosis factor-alpha (TNF-α) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-α are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (VT) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): VT = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): VT = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-α rapidly increased in the lung tissue within 180 min of ventilation with a higher VT with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher VT with pentoxifylline infusion (TNF-α: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1β: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-α produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.