DEFICIENT INTERFERON-ALPHA RESPONSE OF NEWBORNS IN COMPARISON TO ADULTS

Human peripheral blood mononuclear cells (PBMC) respond efficiently to viral infections with interferon (IFN)-alpha production. Using Newcas tle disease virus (NDV) and Sendai virus as inducers, our experiments with purified mononuclear cell populations of healthy adult volunteers showed that monocytes were the main IFN-alpha producers in these syst ems. Using an ELISA, which specifically recognized IFN-alpha2, and a b ioassay, in which all subtypes were detected, IFN-alpha2 was a major s ubtype expressed. Furthermore, IFN-alpha release was higher after indu ction with NDV than after stimulation with Sendai virus. To compare th e IFN-alpha response of adult PBMC to human cord blood mononuclear cel ls the cells were stimulated with NDV or Sendai virus. The IFN-alpha r esponse of cord blood mononuclear cells to Sendai virus was slightly r educed compared to that of adult cells. However, IFN-alpha2 was a majo r subtype produced. In contrast, when cord blood mononuclear cells wer e stimulated with NDV the IFN-alpha release was strongly diminished. F urthermore, IFN-alpha2 was not the major subtype expressed. By in situ hybridization the number of IFN-alpha-producing cells was quantified. We found that 1% of adult PBMC and newborn leukocytes showed detectab le IFN-alpha mRNA after stimulation with either Sendai virus or NDV. I n conclusion, these data suggest that the ability of cord blood mononu clear cells to produce IFN-alpha is diminished compared to adult PBMC. This impaired IFN-alpha response is not based on a reduced number of IFN-alpha-producing cells, but rather due to underlying control mechan isms of the newborns that are different from the regulation of adult P BMC.