Effects of several species of human leukocyte interferon on cytotoxic activity of NK cells and monocytes

Abstract

Ten species of purified human leukocyte interferon were tested for their ability to modulate the cytolytic activity of natural killer (NK) cells and the cytolytic and cytostatic activities of monocytes. The interferon species were tested at several antiviral titers and examined for quantitative differences in their ability to modulate immunological function. At the higher doses of interferon (i.e., greater than 500 units) all of the interferon species demonstrated significant augmentation of cytolysis and cytostasis. However, when low levels (i.e., 10-50 units) of interferon were employed, appreciable differences between the various interferon species were seen. A similar pattern of relative potency among the various species of pure leukocyte interferon was seen for augmentation of cytolysis by monocytes and NK cells. In contrast, a different pattern of relative potency was observed for augmentation of cytostasis. These results demonstrated substantial quantitative differences (as much as 100-fold) in the ability of the various species of human leukocyte interferon to induce significant levels of augmentation of these cell-mediated functions. Such results should have significant impact in choosing a specific interferon species for appropriate clinical trials.

Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression

“…The direct antitumour effects include cell damage (Grander et al, 1993), upregulation of cancer antigen (Guadagni et al, 1989), and delayed action on the cell cycle (Kimchi, 1992). On the other hand, the indirect antitumour actions include activation of natural killer cells (Ortaldo et al, 1983), T cell system (Brinkmann et al, 1993), and macrophages (Uno et al, 1985). It is also possible that both IFN-a and 5-FU reinforce the antitumour action of each other or have additive effects.…”

Impaired interferon production and natural killer cell activation in patients with the skin cancer-prone disorder, xeroderma pigmentosum.

“…NK cell activity was evaluated using "Cr release after a 4-h incubation of the effector and labeled target cells (29). Briefly, PBL were separated from whole blood using lymphoprep gradients (Nycomed, Oslo, Norway).…”

“…Briefly, PBL were separated from whole blood using lymphoprep gradients (Nycomed, Oslo, Norway). PBL isolated at the (29). Variable numbers of effector cells were added to 1 X I05 target cells suspended in 200 ml of complete medium (RPMI 1640 supplemented with 10% FCS, 100 U/ ml penicillin, 100 Ag/ml streptomycin, 0.25,g/ml fungizone, l ug/ml glutamine) with 1 g/ml indomethacin and incubated for 4 h at 37°C in a 5% CO2 atmosphere.…”

Plasmacytoid Dendritic Cells Reduce HIV Production in Elite Controllers

“…Plasmacytoid dendritic cells (pDCs) are innate immune cells that respond to viral infections, producing up to 1,000-fold more alpha interferon (IFN-␣) than other cell types (31) through the stimulation of Toll-like receptor 7 (TLR-7) and TLR-9. The IFN-␣ produced by pDCs not only participates in the inhibition of viral replication but also has an adjuvant effect on different immune cells types, like monocytes (20), natural killer cells (14), and T cells (10), providing a link between innate and adaptive immunity. In the viral infection scenario, HIV stimulation of pDCs induces high levels of IFN-␣ production and the rapid expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), transforming them into IFN-producing killer pDCs (iKpDCs) (5).…”