Abstract 1788 Cytokines in Disease and Therapy Poster Symposium, Monday, 5/3

Pulmonary inflammation has been associated with macrophage release of pro-inflammatory cytokine Interleukin-8 (IL-8) and anti-inflammatory cytokine Interleukin-1 receptor antagonist (IL-1ra). We tested the hypothesis that early inhaled beclomethasone therapy is associated with a reduction in pulmonary inflammation by measuring tracheal aspirate levels of IL-8 and IL-1ra. We also determined whether IL-8 levels on study day 1, predict subsequent need for systemic steroid and development of BPD.

Method: Mechanically ventilated infants <33 weeks gestation and ≤1250 grams birth weight, age 3-14 days, were participants in a randomized, placebo-controlled trial of the safety and efficacy of beclomethasone to prevent BPD. Beclomethasone was tapered over 4 weeks from 40 to 5 mcg/kg/day. Tracheal aspirates were collected and measured for cytokines using ELISA, from infants with no exposure to systemic steroids and still intubated on study days 1, 8, 15, and day of life 28. Interleukin levels were referenced to free secretory component of IgA (FSC), and the ratios were compared between study groups over time using Wilcoxon rank-sum analysis.

Results: Treatment with beclomethasone was associated with lower IL-8 levels in the first two weeks, which was significant on study day 8. IL-1ra levels were also lower in the beclomethasone group and were significant on study day 8 (Table 1). When IL-8 levels on study day 1, were in the mid quartile range (25-75%), suggesting moderate inflammation, beclomethasone therapy was associated with reduced subsequent need for systemic steroid (69 v/s 31%, P=0.002) and development of BPD (64 v/s 36%, P=0.024). Table 1: IL-8 and IL-1ra levels (pg/mcg of FSC) by study group.

Table 1 No caption available
Full size table

Conclusions: These results suggest that early, inhaled beclomethasone therapy is associated with reduction in pulmonary inflammation present early in preterm infants at risk for BPD. Lower levels of IL-1ra in the beclomethasone group suggest that as the inflammation decreases anti-inflammatory cytokines also decrease.