The role of interferon-beta 1 and the 26-kDa protein (interferon-beta 2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor
Van Damme, J.; De Ley, M.; Van Snick, J.; Dinarello, C.A.; Billiau, A.
Journal of Immunology 139(6): 1867-1872
1987
ISSN/ISBN: 0022-1767 PMID: 3305707 Document Number: 294176
This study confirms our earlier finding that human interleukin (IL)-1.beta. exerts an antiviral effect on diploid fibroblasts and on MG-63 osteosarcoma cells. It also extends the observation in that a similar effect was noted on aged but not freshly trypsinized HEp-2 cells, and that not only IL-1.beta. but also IL-1.alpha. and tumor necrosis factor (TNF)-.alpha. exerted similar antiviral effects on cells. The antiviral effects of these cytokines were neutralized by addition to the assay system of an antibody that was specific for interferon (IFN)-.beta.1, indicating that IFN-.beta.1 or a structurally or functionally related substance is involved in the antiviral activity observed. Both IL-1 and TNF were able to induce production of the 26-kDa protein, also known as IFN-.beta.2, hybridoma/plasmacytoma growth factor (HPGF) or B-cell stimulatory factor-2 (BSF-2) and previously proposed as an alternative to IFN-.beta.1 for mediating the antiviral effect of TNF. However, no good correlation was found between the antiviral effects of TNF and its potential to induce production of the 26-kDa protein. Furthermore, the anti-IFN-.beta.1 serum which neutralized the antiviral activity of IL-1 and TNF did not crossreact with the 26-kDa protein. Conversely, the antiviral effect of IL-1 and TNF was only weakly neutralized by an antibody that did react with the 26-kDa protein and showed low cross-reactivity with IFN-.beta.1. These observations, together with the low specific activity of the 26-kDa protein as an antiviral agent (< 105 U/mg protein) provide strong arguments against this protein and in favor of IFN-.beta.1 (or still another IFN-.beta.1-related molecule) as the ultimate mediator of the antiviral effect of IL-1 and TNF.