Activation of Nuclear Factor-?B and Its Suppression by Dexamethasone in Polymorphonuclear Leukocytes: Newborn Versus Adult

Polymorphonuclear leukocytes (PMN) of the newborn, to a greater extent than those of the adult, have the ability to amplify PMN recruitment to an inflammatory site by their own release of IL-8, and this process is inhibited by dexamethasone. The aim of the present study was to determine whether the regulation of nuclear factor-?B (NF-?B) could explain the previous observations. NF-?B is a transcription factor pivotal for expression of genes encoding inflammatory cytokines such as IL-8, but NF-?B has not been previously studied in the PMN of the newborn. NF-?B activation was measured by an electrophoretic mobility shift assay in nuclear extracts prepared from PMN isolated from adults and cord blood from newborns. Two distinct molecular forms of NF-?B were identified after tumor necrosis factor-a stimulation; this included the previously characterized p50/65 heterodimer and a newly identified p50/50 homodimer. Both NF-?B dimers were activated by tumor necrosis factor-a to significantly higher levels in the neutrophil of the newborn versus adult. An additional new finding was that pretreatment of PMN with dexamethasone (10-7M, therapeutic range) inhibited activation of both NF-?B complexes in both the newborn and the adult PMN. We conclude that the increased activation of NF-?B by the PMN of the newborn may play an important role in neonatal inflammatory reactions. Eventually, specific targeting of NF-?B activation in the neutrophil may be an effective molecular approach for the treatment of neutrophil-mediated disorders in the newborn.