Divergent effects of interleukin-10 on cytokine production by mononuclear phagocytes and endothelial cells.
Interleukin-10 (IL-10), a product of T helper type 2 (TH2) cells and monocytes, inhibits cytokine production in mononuclear phagocytes. Given the similarities and interrelationship between cells of the monocyte-macrophage lineage and endothelial cells, we examined the effects of IL-10 on vascular endothelium. Murine IL-10 induced low levels of IL-6 production and amplified induction of IL-6 by lipopolysaccharide (LPS) or IL-1 in the murine tEND.1 endothelioma line, used for these studies because it retains properties of normal endothelium. The effect was more evident after prolonged (48-72 h) exposure to IL-10. IL-10 had similar activity on other endothelioma lines, whereas it inhibited IL-6 production by peritoneal macrophages. Induction and amplification of cytokine production by IL-10 was associated with higher levels of mRNA, which were maintained longer (up to 48 h) than in controls. In addition to IL-6, murine IL-10 induced or amplified expression of the chemoattractant cytokines monocyte chemotactic protein-1 (MCP-1) and KC. Human IL-10 inhibited IL-6 release by LPS-stimulated human peripheral blood mononuclear cells, whereas it did not interfere with cytokine production by LPS- or IL-1-stimulated human umbilical vein endothelial cells. The selective inhibitory action of IL-10 on mononuclear phagocytes versus endothelial cells may play a role in the pathophysiology of TH2-directed responses.
Sironi
M
M
Centro Daniela e Catullo Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Muñoz
C
C
Pollicino
T
T
Siboni
A
A
Sciacca
F L
FL
Bernasconi
S
S
Vecchi
A
A
Colotta
F
F
Mantovani
A
A
D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10