Differential Regulation of IL-8 by IL-1β and TNFα in Hyaline Membrane Disease
ABSTRACT Mechanisms that regulate cytokine-mediated inflammation in the lungs of preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lavage samples were obtained from preterm newborns with hyaline membrane disease over a 28-day period. Bronchoalveolar lavage cell cytokine relationships were evaluated and the differential regulation of IL-8 by IL-1 and TNF was studied in a short-term culture system. In vivo, IL-8 and IL-l protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1 antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNF antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1 and anti-TNF antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-l antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1 and TNF regulate IL-8 expression in the lungs of preterm infants.
Article: Inhaled corticosteroid therapy reduces cytokine levels in sputum from very preterm infants with chronic lung disease.[show abstract] [hide abstract]
ABSTRACT: To evaluate the effects of inhaled corticosteroid therapy and high-frequency oscillatory ventilation (oscillation) on preterm infants with chronic lung disease (CLD). Ten infants with CLD who received inhaled corticosteroid therapy were enrolled. Week 1 was defined as the first week of therapy. The concentrations of interleukin (IL)-8, tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-10 and IL-12p70 in serial sputum specimens from the infants were determined using a cytometric bead array. The sputum concentrations of IL-8 obtained from the infants during week 3-4 were significantly lower than those obtained before therapy and during week 1-2. The sputum concentrations of TNF-alpha, IL-6 and IL-10 during week 3-4 were significantly lower than the concentrations during week 1-2. The ratio of IL-8 levels during week 1-2 to those before therapy in infants who received oscillation (n = 4) was significantly lower than in those who received intermittent mandatory ventilation (n = 6). Inhaled corticosteroids may be associated with a decrease in pro-inflammatory cytokine levels in sputum from infants with CLD from 2 weeks after the start of therapy. Our further investigations suggest that therapy with oscillation modulated airway inflammation earlier than therapy with intermittent mandatory ventilation.Acta Paediatrica 02/2009; 98(1):118-22. · 2.07 Impact Factor