EFFECTS OF INTERFERON-ALPHA (IFN-ALPHA) ADMINISTRATION ON LEUKOCYTES IN HEALTHY HUMANS

Plasma concentrations of IFN-alpha are increased in several inflammato ry conditions. Several lines of evidence indicate that IFN-alpha has a nti-inflammatory properties. To study the effects of IFN-alpha on leuc ocyte subsets and activation and on cytokines, we administered IFN-alp ha (rhIFN-alpha 2b; 5 x 10(6) U/m(2)) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in ci rculating leucocytes and parameters for neutrophil and monocyte activa tion. After administration of IFN-alpha, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocyt es, basophils and eosinophils showed a sustained decrease. IFN-alpha a dministration was also associated with neutrophil activation, reflecte d in an increase in the plasma concentrations of elastase-alpha(1)-ant itrypsin complexes and lactoferrin. Serum neopterin, a marker for mono cyte activation, was significantly increased 10 h after administration of IFN-alpha. IFN-alpha significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TN F) remained undetectable, plasma concentrations of soluble TNF recepto rs p55 and p75 increased after IFN-alpha administration. We conclude t hat IFN-alpha induces multiple alterations in the distribution and fun ctional properties of leucocytes. IFN-alpha exerts pro- as well as ant i-inflammatory effects within the cytokine network.