INDUCTION OF MACROPHAGE-INFLAMMATORY PROTEIN 1-ALPHA (MIP-1-ALPHA) BYINTERFERON-ALPHA

The biological functions of macrophage-inflammatory protein 1 alpha (M IP-1 alpha) include the regulation of inflammatory processes and the i nhibition of early hematopoiesis. We investigated the regulation of MI P-1 alpha in various cell types in response to IFN-alpha and IL-4 by m RNA analysis and examination of MIP-1 alpha protein levels in culture supernatants. In peripheral blood mononuclear cells (PBMNCs) and purif ied monocytes, IFN-alpha, induced MIP-1 alpha mRNA expression and stim ulated MIP-1 alpha secretion in LPS-activated monocytes to almost twic e the value observed with LPS alone, whereas IL-4 caused a reduction b y 80-95%. The stimulatory effect of IFN-alpha on MIP-1(alpha) producti on appeared to be dominant over its inhibition by IL-4. This effect wa s most pronounced after prolonged incubation periods. In fibroblasts o btained from human foreskin, IFN-alpha in combination with IL-1 stimul ated MIP-1 alpha secretion to more than three times the level obtained with IL-1. Stimulation of MIP-1 alpha expression by IFN-alpha may ind irectly influence inflammatory processes and the regulation of early h ematopoiesis.