title: Contrasting effects of interferon-gamma and interleukin-4 on neopterin generation from human adherent monocytes.
abstract: The production of neopterin is closely correlated with activation of cell-mediated immunity. Neopterin appears to be produced by human macrophages specifically stimulated with interferon-gamma (IFN-gamma). Interleukin-4 (IL-4), a B and T stimulatory factor, has recently been shown to inhibit monocyte/macrophage functions, including the ability to suppress monocyte-generated cytokines. In this report we confirmed previous studies that identified the monocyte/macrophage as the main producing cell among human blood cells and that secretion is stimulated by IFN-gamma and lipopolysaccharides (LPS). IL-4 inhibits the generation of neopterin from unstimulated monocytes. This inhibitory effect was dose dependent and occurred at concentrations lower than 0.01 ng/ml. However, IL-4 had only a minimal inhibitory effect on LPS-induced generation of neopterin and could not reverse IFN-gamma-induced neopterin secretion from adherent monocytes. Furthermore, we report that LPS induced IFN-gamma production in monocyte culture. This production is strongly inhibited by IL-4 treatment. These findings indicate that IL-4 can regulate the synthesis of neopterin by adherent blood mononuclear cells and provide further evidence that LPS-induced neopterin in macrophages may act by IFN-gamma-independent mechanisms.
authors: Department of Urology, Osaka University Hospital, Japan.
authors: A
authors: A
authors: Moutabarrik
authors: S
authors: S
authors: Takahara
authors: M
authors: M
authors: Namiki
authors: H
authors: H
authors: Kameoka
authors: T
authors: T
authors: Seguchi
authors: K
authors: K
authors: Yokokawa
authors: Y
authors: Y
authors: Takano
authors: T
authors: T
authors: Sonoda
authors: M
authors: M
authors: Ishibashi
authors: D
authors: D
authors: Zaid
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D002448:Cell Adhesion; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019798:Neopterin
chemical_list: D008070:Lipopolysaccharides; D015847:Interleukin-4; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma