Serum levels of seven cytokines in premature ventilated newborns: correlations with old and new forms of bronchopulmonary dysplasia.

OBJECTIVE: In addition to the previous classification of chronic lung disease (CLD) O2 dependency at 36 weeks of postmenstrual age, a new definition of CLD has recently been proposed: new bronchopulmonary-dysplasia (BPD). This uses total duration of O2 supplementation and positive pressure requirements to delineate three degrees of severity (mild, moderate, and severe) according to the respiratory status at 36 weeks postmenstrual age. We analyzed the balance of serum proinflammatory and profibrotic/angiogenic cytokine concentrations in relation to CLD and the new BPD definition. DESIGN AND SETTING: Descriptive study in a third-level neonatal ICU. PATIENTS: Thirty-one preterm neonates with a gestational age of 24-29 weeks were studied to evaluate their serum cytokine concentration; they were previously enrolled in a randomized clinical trial to compare the effects of high-frequency oscillatory ventilation vs. intermittent mandatory ventilation in terms of pulmonary mechanics and lung cytokines. Serum samples were collected on days 1, 3, and 5 after birth until extubation to detect the levels of three proinflammatory cytokines plus four profibrotic/angiogenic cytokines, and correlations were examined to old CLD and new BPD. Ventilation treatments were distributed homogeneously between the groups and did not interfere with the results presented here. RESULTS AND CONCLUSIONS: Old CLD development, mainly corresponding to the moderate/severe forms of new BPD, was associated with increased proinflammatory and profibrotic/angiogenic cytokines, while mild forms of new BPD were characterized only by increases in profibrotic/angiogenic cytokines, suggesting a different balance of two pathogenic mechanisms in different phases of the disease.

Comparison of serum levels of seven cytokines in premature newborns undergoing different ventilatory procedures: high frequency oscillatory ventilation or synchronized intermittent mandatory ventilation.

OBJECTIVE: The severity of pulmonary dysfunction and subsequent development of chronic lung disease (CLD) in preterm neonates depends on several factors, among them oxygen administration. The aim of this report is to compare the effects of high-frequency, oscillatory ventilation (HFOV) versus synchronized, intermittent, mandatory ventilation (sIMV) on serum cytokine levels (IL-6, IL-8, IL-10, MCP-1, PDGF-BB, VEGF and TGF-beta1) and ventilator indices during the first week of life. Moreover, CLD development and several other outcomes were compared between the two groups. DESIGN: Randomized clinical trial. SETTING: Third level NICU. PATIENTS: 40 preterm neonates with a gestational age between 24 and 29 weeks were randomly (20 per group) assigned to one of the two, above-mentioned ventilation strategies within 30 minutes of birth. MEASUREMENTS AND RESULTS: At 1, 3 and 5 days, neonates were monitored by means of ventilator indices and levels of seven pro-inflammatory or anti-inflammatory (pro-fibrotic) cytokines in serum. No clinical or biochemical differences were observed at baseline. The neonates assigned to HFOV benefited from early and sustained improvement in gas exchange, with earlier extubation and lower incidence of CLD, as compared to the neonates assigned to sIMV treatment, and showed a significant reduction of serum IL-6, IL-8 and IL-10 over time only when the HFOV treatment was administered. In addition, at days 3 and 5, the IL-6 levels were significantly lower in the HFOV group as compared to sIMV patients. CONCLUSIONS: The results of this randomized clinical trial support the hypothesis that early use of HFOV, combined with an optimum volume strategy, has a beneficial effect, reducing serum levels of pro-inflammatory cytokines and consequently the acute phase leading to lung injury.