Effects of interferon-alpha (IFN-α) administration on leucocytes in healthy humans

Abstract

SUMMARYPlasma concentrations of IFN-a are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-a has anti-inflammatory properties. To study the effects of IFN-a on leucocyte subsets and activation and on cytokines, we administered IFN-a (rhIFN-a2b; 5 × 10 6 U/m 2 ) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in circulating leucocytes and parameters for neutrophil and monocyte activation. After administration of IFN-a, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-a administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastasea 1 -antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-a. IFN-a significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma concentrations of soluble TNF receptors p55 and p75 increased after IFN-a administration. We conclude that IFN-a induces multiple alterations in the distribution and functional properties of leucocytes. IFN-a exerts pro-as well as anti-inflammatory effects within the cytokine network.

Induction of CD83+CD14+ Nondendritic Antigen-Presenting Cells by Exposure of Monocytes to IFN-α

“…It is possible therefore that additional factors including adhesion molecules, which we found up-regulated on IFN-MO, may play a role in monocytes homing in LNs. In line with this hypothesis, the number of peripheral blood monocytes decreases while serum neopterin (a monocyte activation marker) increases upon IFN-␣ injection (31). Notably, the "maturing" effect of IFN-␣ we report herein was rapid, and 24 h priming was sufficient to maintain the mature phenotype for 3 days.…”

“…Numerous papers show a promoting effect of type I IFNs on DC generation (21,(23)(24)(25)(26)(27), but an inhibitory effect has also been reported (22,28,29). Even though blood and tissue resident cells can be exposed to high levels of type I IFNs during IFN-␣ therapy (14,30,31) or viral infections (11,32,33), to our knowledge the effects of type I IFNs on monocytes have never been studied in the absence of other cytokines. To this end, we investigated the effects of IFN-␣ on PBMC or on purified monocytes in terms of DC differentiation and function.…”

Treatment with interferon-alpha preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors (CFU-GM) from patients with chronic myeloid leukemia but spares normal CFU-GM.

“…The AUC measurement that we have devised relates to amplification by the whole CFU-GM population (see Methods) and was significantly suppressed in CML cell cultures but not in normal cell cultures. It is relevant that IFN-␣ was effective at concentrations corresponding to plasma levels, which occur physiologically or can be induced pharmacologically (28)(29)(30)(31). Therefore, this result provides the first demonstration of a differential effect of IFN-␣ in vitro at concentrations that may be expected to occur in vivo.…”

The clinical and physiological spectrum of interferon-alpha induced thyroiditis: Toward a new classification

“…87 IFN␣ also has the ability to affect leukocyte function. It has been shown to enhance the activity of lymphocytes, macrophages, and NK cells, 2,85,88,89 and to stimulate neutrophil and monocyte activation. 85 IFN␣ can induce the release of other cytokines.…”