Abstract • 112

One of the most consistently observed defects in the host defense system of the human neonate is in the activation and movement of neutrophils toward a chemotactic stimulus. Defective neutrophil chemotactic movement most likely contributes to skin, mucous membrane, lung and tissue infections in the human neonate. We have observed significant depression of neutrophil chemotactic activity in human neonates associated with defective membrane potential changes and intracellular calcium ion release. These alterations result in decrease mobility of cell surface receptors and alterations in size and shape of the cells. A number of these abnormal parameters in the neonatal neutrophil are corrected following incubation of the cells with the TH1 type cytokine, interferon γ. Recent studies from our laboratory indicate that transcription, translation and secretion of IFNγ as well as its major inducer IL-12 is decreased in neonatal cells compared to those from adults. Alterations in these critical proinflammatory cytokines likely contribute to inadequate influx of inflammatory cells into the site of microbial invasion in human neonates, leading to the severe and often overwhelming infection that neonates may suffer.

Funded, in part, by U.S. Public Health Service Grant AI13150.