IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.
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.
Miyashita
Hiroyuki
H
Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
Katayama
Naoyuki
N
Fujieda
Atsushi
A
Shibasaki
Tetsunori
T
Yamamura
Kentaro
K
Sugimoto
Yuka
Y
Miyata
Eri
E
Ohishi
Kohshi
K
Nishii
Kazuhiro
K
Masuya
Masahiro
M
Shiku
Hiroshi
H
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
D000970:Antineoplastic Agents; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor