Lipopolysaccharide-induced tumor necrosis factor-alpha and IL-10 production by lung macrophages from preterm and term neonates.

Lung injury in preterm neonates with respiratory failure has been attributed to persistent inflammation, which is likely to involve lung macrophages (LM). The study objective was to investigate LM during the first 8 d of life from preterm infants (n = 19), using term infants (n = 11) with respiratory failure as control subjects. LM percentages from mixed-cell suspensions produced from tracheobronchial lavage were calculated. A postnatal increase in the mean LM concentration was demonstrated within the preterm group (p = 0.01), which was greater in comparison to that from the term group (p < 0.01). Regression analyses were significant for direct relationships between LM concentrations and ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha and IL-10 production (r = 0.93 and r = 0.63, respectively), establishing LM as the source of these cytokines. Comparative analyses demonstrated that the ability of preterm versus term LM to produce tumor necrosis factor-alpha was nearly identical; in contrast, a trend toward diminished levels of IL-10 expression in the preterm group was observed (p = 0.06). Thus, although studies have shown that LM precursors (i.e. cord blood monocytes) produce less tumor necrosis factor-alpha in preterm versus term infants, the present data strongly suggest that this relationship does not hold postnatally with respect to terminally differentiated LM in sick neonates. Overall, the data are consistent with a pro- versus antiinflammatory imbalance that may bear functional significance on the pathogenesis of chronic lung disease.