Potentiation of interferon-induced indoleamine 2,3-dioxygenase mRNA in human mononuclear phagocytes by lipopolysaccharide and interleukin-1

Previous studies have shown that interleukin-l (IL-1) enhances interferon (IFN)-gamma-induced indoleamine 2,3-dioxygenase (IDO) enzymatic activity in human monocyte-derived macrophages by increasing expression of IDO mRNA, The objectives of this study were to see if IL-1 also enhances IFN-beta-induced IDO activity by increasing specific mRNA expression and to determine if lipopolysaccharide (LPS) enhances IFN-induced IDO activity in a similar manner, Macrophages were treated with combinations of IFN-beta or IFN-gamma as inducer and LPS or IL-1 as potentiator, After 48 h, IDO mRNA expression was assessed by RT-PCR, and IDO activity was determined by HPLC, LPS alone induced IDO mRNA expression and also increased IDO mRNA expression induced by either type of IFN, Furthermore, IL-1 enhanced IFN-beta-induced IDO mRNA expression, When IDO mRNA was assessed 6 h after treatment, mRNA was detected at concentrations of IFNs or potentiator or both in which enzymatic activity at 48 h was undetectable, Thus, although the mechanism of potentiation of IFN-induced IDO by LPS and by IL-1 involves increased expression of IDO mRNA, it appears that temporal differences in IDO mRNA expression are also important.