THE EFFECTS OF IL-10 ON PROINFLAMMATORY CYTOKINE EXPRESSION (IL-1-BETA AND IL-8) IN HYALINE-MEMBRANE DISEASE (HMD)

Deficient expression of the counterregulatory cytokine IL-10 by lung i nflammatory cells may facilitate chronic inflammation and the pathogen esis of hyaline membrane disease (HMD), in premature infants. To deter mine if pathways which regulate proinflammatory cytokines in response to human recombinant IL-10 (rIL-10) were functional in the lungs of th ese neonates, bronchoalveolar lavage (BAL)-derived lung inflammatory c ells (predominantly macrophages and neutrophils) from infants with HMD were cultured in the presence of lipopolysaccharide (LPS) and increas ing concentrations of (rIL-10), The expression of IL-1 beta and IL-8 p rotein was assessed 24 h later. IL-10 protein was also measured from t he BAL aspirates of these newborns at 4-day intervals over the first m onth of life. In cell culture IL-1 beta expression was inhibited by rI L-10 in a dose-dependent fashion while IL-8 expression was inhibited b y higher concentrations of rIL-10. IL-10 protein was undetectable from BAL fluid of the premature infants sampled over 28 days. The results demonstrate that lung inflammatory cells, which do not express IL-10 i n vivo, are capable of responding to rIL-10 in cell culture with reduc tion of IL-1 beta and IL-8 expression. These data support the rational e for the development of rIL-10 as a potential anti-inflammatory agent in the treatment of HMD. (C) 1998 Academic Press.