title: IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.
abstract: Interleukin (IL)-4 and IL-10 have a wide variety of activities in the immune system. We re-evaluated the action of IL-4 and IL-10 on human blood monocytes, myeloid dendritic cell (DC1) precursors, using a serum-free culture system. Both IL-4 and IL-10 inhibited the survival of CD14+ monocytes supported by granulocyte-macrophage colony-stimulating factor in a dose-dependent manner. When IL-4 and IL-10 were combined, they had synergistic effects at low doses and induced a profound suppression of CD14+ monocyte survival. When the optimal timing was determined, the exposure to IL-4 and IL-10 for the initial 2 days was essential for suppression of survival of CD14+ monocytes. Annexin V/propidium iodide staining indicates that the suppression of CD14+ monocyte survival induced by IL-4 and IL-10 results from apoptosis. Tumor necrosis factor-alpha and lipopolysaccharide abrogated the effects of IL-4 and IL-10 on CD14+ monocytes, albeit incompletely. Thus, IL-4 in synergy with IL-10 negatively regulates the survival of DC1 precursor monocytes by inducing their apoptosis, which is modulated by factors such as tumor necrosis factor-alpha and lipopolysaccharide. Our data suggest the primary activities of IL-4 and IL-10 in DC1-mediated immune responses.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyashita
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujieda
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamamura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Miyata
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018929:Cell Culture Techniques; D002470:Cell Survival; D003713:Dendritic Cells; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes
chemical_list: D000970:Antineoplastic Agents; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor