Potentiation of Interferon-Induced Indoleamine 2,3-Dioxygenase mRNA in Human Mononuclear Phagocytes by Lipopolysaccharide and Interleukin-1

Abstract

Previous studies have shown that interleukin-1 (IL-1) enhances interferon (IFN)-γ-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-β-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-β or IFN-γ 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-β-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.