Differential regulation of IL-8 by IL-1beta and TNFalpha in hyaline membrane disease

J Clin Immunol. 1998 Jan;18(1):71-80. doi: 10.1023/a:1023244005765.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Hyaline Membrane Disease / immunology*
  • Infant, Newborn
  • Infant, Premature
  • Interleukin-1 / analysis
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology*
  • Interleukin-8 / analysis
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Leukocyte Count
  • Leukocytes / drug effects
  • Lipopolysaccharides / pharmacology
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*


  • Antibodies, Blocking
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha