Differential regulation of IL-8 by IL-1β and TNFα in hyaline membrane disease

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 beta and TNF alpha was studied in a short-term culture system. In vivo, IL-8 and IL-1 beta protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1 beta antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNF alpha antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1 beta and anti-TNF alpha antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-1 beta antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1 beta, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1 beta and TNF alpha regulate IL-8 expression in the lungs of preterm infants.