Influence of various factors on interferon-alpha production in cultures of human leukocytes

Inducer-specific gene loci and sex are known to play a role in the regulation of interferon-alpha (IFN-alpha) production in mice. Because little is known about the genetic control of the IFN-alpha system in man, we investigated the IFN-alpha production of 468 individuals by culturing peripheral blood with Newcastle disease virus (NDV) or Sendai virus (SDV). The IFN alpha release of different donors varied over a wide range. However, IFN-alpha production of 7 donors showed a donor-specific response over a period of 4 months, which led us to classify some donors as high and low responders. The amounts induced by NDV correlated positively to those induced by SDV. The donor's sex did not alter the IFN-alpha production significantly. The subjects were between 1 and 90 years in age. Highest IFN-alpha levels were obtained in children, followed by a gradual decline with age. Using a specific IFN-alpha-2 enzyme-linked immunosorbent assay (ELISA) and a bioassay, which detects all subtypes, our data showed that the net IFN-alpha production decreased with age. For further studies, we selected 17 low producers and 17 high producers. To analyze a possible influence of major histocompatibility complex (MHC) on IFN-alpha production, the HLA genotypes of 13 low producers and 12 high producers were determined. Here, no correlation between high or low production and HLA genotype was detectable.