Increase in Interleukin (IL)-1β and IL-6 in Bronchoalveolar Lavage Fluid Obtained from Infants with Chronic Lung Disease of Prematurity

Abstract

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1β and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants(median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four(38 wk, 2690 g) control infants. IL-1β and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1β, 4.6 versus 1.1 ng/mL,p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p< 0.05). Immunocytochemistry of lavage cells for IL-1β, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1β and IL-8 mRNA was similar in both groups. These results suggest that IL-1β, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.