INTERFERONS AND THE COLONY-STIMULATING FACTOR-IL-3 AND FACTOR-GM-CSF ENHANCE THE IFN-ALPHA RESPONSE IN HUMAN BLOOD LEUKOCYTES INDUCED BY HERPES-SIMPLEX VIRUS

Human peripheral blood mononuclear cells (PBMC) were stimulated to produce interferon-alpha (IFN-alpha) by glutaraldehyde-fixed Herpes simplex virus type 1 (HSV)-infected WISH amnion cells in vitro. Different cytokines were included during the stimulation and tested for their ability to enhance the IFN-alpha response which occurs in the natural IFN-alpha producing (NIP) leucocytes. The total production of IFN-alpha and the numbers of IFN-alpha producing cells (IPCs) were increased by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Their most marked effect was to reduce the time required for induction of the IPC by the HSV-infected cells, thereby causing both an earlier peak of IPC numbers and secretion of IFN-alpha. Addition of IFN-alpha-2b did not alter the kinetics of the IFN-alpha response in the same way as the two CSFs, but instead generally increased the IPC numbers and the production of IFN-alpha. The IL-3 and GM-CSF, especially in combination with IFN-alpha, had the most pronounced enhancing effects on IPC numbers when PBMC were induced at low cell concentrations. The cytokines IL-1, IL-2, IL-4, IL-6 or tumour necrosis factor-alpha (TNF-alpha) had no detectable effects on the IFN-alpha response. The results suggest that cytokines such as the CSFs and IFNs may be involved in the regulation of NIP cell functions.