Interferon-alpha and interferon-gamma down-regulate the production of interleukin-8 and ENA-78 in human monocytes

The two chemotactic cytokines interleukin-8 (IL-8) and epithelial neutrophil activating protein 78 (ENA-78) were recently shown to be potent chemoattractants and activators of neutrophil function and to be present in certain inflammatory diseases. We have studied the effects of recombinant and natural interferon-alpha (IFN-alpha) and of recombinant interferon gamma (rIFN-gamma) on the production of IL-8 and ENA-78 in lipopolysaccharide- and interleukin-1-stimulated human monocytes. Both types of interferons showed a strong, concentration-dependent inhibition of neutrophil-stimulating bioactivity. Similarly, the secretion of IL-8 and ENA-78 was also inhibited by up to 73%. Northern blot experiments demonstrated that IFN-alpha decreases the steady-state levels of IL-8 and ENA-78 mRNA in monocytes, suggesting that IFN-alpha as well as IFN-gamma may control the expression of neutrophil chemotactic cytokines at the mRNA level.