Article Text

High concentrations of GRO-α and MCP-1 in bronchoalveolar fluid of infants with respiratory distress syndrome after surfactant
  1. DAVID P INWALD,
  2. KATE COSTELOE,
  3. SIMON H MURCH
  1. Garden House Children’s Unit
  2. Royal London Hospital
  3. Whitechapel Road
  4. E1 1BB

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    Editor—Recent work has related the severity of lung damage after neonatal respiratory distress syndrome (RDS) to the early inflammatory response and the degree of matrix degradation.1 2Although treatment with exogenous surfactant reduces the incidence of bronchopulmonary dysplasia (BPD), it is not known whether it attenuates this inflammatory response.

    This response has largely been investigated by looking at cells, cytokines, and chemokines in the bronchoalveolar lavage fluid (BAL) of ventilated infants. Increased concentrations of the macrophage cytokines tumour necrosis factor α and interleukin-1β, the CC chemokine MIP-1α and the CXC chemokine IL-8 have all been detected in the BAL fluid of infants who subsequently develop BPD.1 3Treatment with dexamethasone decreases inflammatory cell numbers and the concentrations of pro-inflammatory mediators, as well as improving clinical outcome, although at considerable metabolic cost.1 3

    The CC chemokine MCP-1 and the CXC chemokine GRO-α have not been investigated in RDS. They may both have a central role in pulmonary inflammation and they have been implicated in the pathogenesis of experimental pulmonary fibrosis and adult fibrotic disease.4 5 We measured these chemokines in the BAL fluid of 15 infants with RDS (median birthweight 1001 g, range 700–1340 g; gestation 27 weeks, range 25–31 weeks), who had been treated with early exogenous surfactant. BAL was performed in the first six days of life, after surfactant treatment, as described before.3 Of the 15 infants, 10 had been treated with porcine surfactant (Curosurf, Serono) and five had been treated with synthetic surfactant (Exosurf, Wellcome) None had received postnatal steroids at the time of study. Ten of the infants subsequently became oxygen dependent at 36 weeks of equivalent gestation, fulfilling current criteria for the diagnosis of BPD.

    The median concentration of MCP-1 was 14.72 ng/ml (95% CI 10.83–19.08) and of GRO-α was 4.32 ng/ml (2.80–6.91). These concentrations are far in excess of those found in any previous study of pulmonary inflammation.4 5 Our results suggest that the intense early pulmonary inflammatory response in RDS is not attenuated effectively by surfactant treatment, and they confirm that four potent chemokines are produced in high concentration in this condition. Work in animal models has shown that pre-treatment with cytokine antagonists can prevent experimental pulmonary fibrosis, whereas subsequent treatment is ineffective. RDS is probably the only human inflammatory condition in which such pretreatment is possible. We suggest that the time has come for similar studies of cytokine antagonism in infants ventilated for RDS.

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