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Plasma concentrations of IFN-α are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-α has anti-inflammatory properties. To study the effects of IFN-α on leucocyte subsets and activation and on cytokines, we administered IFN-α (rhIFN-α2b; 5 × 106 U/m2) 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-α neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-α administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastase α1-antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-α. IFN-α 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-α administration. We conclude that IFN-α induces multiple alterations in the distribution and functional properties of leucocytes. IFN-α exerts pro- as well as anti-inflammatory effects within the cytokine network. [ABSTRACT FROM AUTHOR]