Interferons and the Colony‐Stimulating Factors IL‐3 and GM‐CSF Enhance the IFN‐α Response in Human Blood Leucocytes Induced by Herpes Simplex Virus

Abstract

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.

Production of Interleukin‐4, Interferon (IFN)‐γ and IFN‐α in Human Immunodeficiency Virus‐1 Infection: An Imbalance of Type 1 and Type 2 Cytokines may Reduce the Synthesis of IFN‐α

“…In their experiments, adherent cells were pretreated overnight with IL-2, whereas we induced PBMCs to produce IFN-a in the presence of IL-2, which may account for the differences in the results. In our study, the HSV-1-induced IFN-a response could be enhanced by IFN-g but not by IL-2, which agrees with previous reports [23].…”

“…Our results agree with those of other authors who described a down-regulation of IFN-a/b production by IL-4 in PBMC, monocytes and macrophages and by IL-13 in monocytes [41][42][43][44]. However, it has been reported that IL-4 affected IFN-a response in PBMCs stimulated by SV but not by HSV-1 [23]. The discrepancy between the production of IFN-a-in HSV-1-stimulated cultures in our work and in other studies may be due to experimental conditions since we used supernatants of HSV-1-infected cells as activators whereas other authors used HSV-1-infected cells as stimuli [23].…”

“…However, it has been reported that IL-4 affected IFN-a response in PBMCs stimulated by SV but not by HSV-1 [23]. The discrepancy between the production of IFN-a-in HSV-1-stimulated cultures in our work and in other studies may be due to experimental conditions since we used supernatants of HSV-1-infected cells as activators whereas other authors used HSV-1-infected cells as stimuli [23]. The effects of IL-2 on SVand HSV-1-induced IFN-a response appeared to be at least partially different in our experiments.…”

“…It has been shown that it specifically promotes differentiation towards the type-1 immune response [19,20]. In addition, various cytokines enhance or down-regulate the virus-induced production of IFN-a in human blood leucocytes [21][22][23]. Together these data indicate that there may be an interaction between natural and adaptive immune responses.…”

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

“…IL-3 and GM-CSF have been described to promote the production of IFN-␣ in response to HSV (26). We found that both pDC and cDC produced more IFN-␣ to HSV-1 in the combined presence of IL-3 and GM-CSF (Fig.…”