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

• Published in: Brazilian journal of medical and biological research Vol. 36; no. 10; pp. 1349 - 1357
• Main Authors: Oliveira-Junior, I S, Pinheiro, B V, Silva, I D C G, Salomão, R, Zollner, R L, Beppu, O S
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Divulgação Científica 01-10-2003
• Subjects: Acute lung injury; Animals; BIOLOGY; Blood Gas Analysis; Bronchoalveolar Lavage; Inflammation; Interleukin-1 - blood; Lung Volume Measurements; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Pentoxifylline; Pentoxifylline - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Rats; Rats, Wistar; Respiration, Artificial; Respiratory Distress Syndrome, Adult - drug therapy; Tidal Volume; Tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - drug effects; Pentoxifylline; Acute lung injury; Tumor necrosis factor-alpha; Inflammation
• ISSN: 0100-879X; 1414-431X; 0100-879X; 1414-431X
• DOI: 10.1590/S0100-879X2003001000011

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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 (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 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-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2+/-90.9 and BAL, 118.2+/-82.1; IL-1 : plasma, 45.2+/-42.7 and BAL, 50.2+/-34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.