PROLONGED HYPERVENTILATION IS REQUIRED FOR RELEASE OF TUMOR-NECROSIS-FACTOR A BUT NOT IL-6

Mechanical stress induced by artificial ventilation can lead to lung d amage, including edema formation, rupture of alveolar walls and accumu lation of neutrophils. Recently we demonstrated that hyperinflation st imulates expression and release of tumor necrosis factor alpha (TNF) a nd interleukin-6 (IL-6) into the perfusate of the isolated mouse lung. In the present study we investigated whether continuous stimulation b y hyperinflation is needed for release of these cytokines. We compared the effect of 30 minutes of hyperinflation (-25 cm H2O) followed by 1 20 min of normal ventilation (-10 cm H2O) to lungs that were continuou sly hyperventilated for 150 min. While TNF release was enhanced only a s long as hyperinflation was maintained, 30 min of hyperventilation wa s sufficient to stimulate release of IL-6 for the following 120 min. T hese data show that even short periods of hyperinflation may elicit re lease of IL-6, but also that TNF and IL-6 are released independently. We suggest that release of cytokines during mechanical ventilation may contribute to the side effects of mechanical ventilation.