DIFFERENTIAL REGULATION OF IL-8 BY IL-1-BETA AND TNF-ALPHA IN HYALINE-MEMBRANE DISEASE

Mechanisms that regulate cytokine-mediated inflammation in the lungs o f preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lava ge samples were obtained from preterm newborns with hyaline membrane d isease over a 28-day period. Bronchoalveolar lavage cell cytokine rela tionships 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 v ivo, IL-8 and IL-1 beta protein levels correlated closely with each ot her and with macrophage counts. In cell culture, exogenous anti-IL-1 b eta antibody led to a 40% maximum inhibition (approximately) of IL-8 p roduction by lipopolysaccharide stimulated lung inflammatory cells. Co mparable 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 pro duction beyond that achieved by anti-IL-1 beta antibody alone. These r esults, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1 beta, and IL-8 cell cytokine pa thway. The results also suggest that factors other than IL-1 beta and TNF alpha regulate IL-8 expression in the lungs of preterm infants.