Interleukin-10 decreases tumor necrosis factor alpha and beta in alloreactions induced by human lung dendritic cells and macrophages.
Human lung dendritic cells (DC) are considerably more potent than alveolar macrophages (AM) in inducing allogeneic T-cell proliferation. Tumor necrosis factor (TNF) alpha and beta produced during alloreaction are likely to be major inflammatory cytokines involved. Their concentrations were therefore analyzed during the interaction of AM or DC with allogeneic T cells. TNF alpha and TNF beta levels were respectively three-fold and sevenfold higher in the presence of DC as compared with AM. Cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor beta (TGF beta) were compared as to their ability to control DC-induced T-cell proliferation as well as TNF alpha or TNF beta production. IL-10 had the unique capacity of reducing both TNF alpha and TNF beta production by 60 +/- 5% (mean +/- SEM) and 63 +/- 12%, respectively, while inhibiting T-cell proliferation by only 32 +/- 23%. IL-4 and TGF beta increased the release of TNF beta by 275 +/- 22% and 95 +/- 32%, respectively, while that of TNF alpha was slightly decreased or unchanged. An additive effect of IL-10 to cyclosporine was found for all three parameters studied. Interaction between CD4 or CD8 with DC was affected similarly by IL-10. Part of this effect could be due to the downregulation of class I and class II major histocompatibility complex expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicod
L P
LP
Respiratory Division, University Hospital, Geneva, Switzerland.
el Habre
F
F
Dayer
J M
JM
Boehringer
N
N
D002469:Cell Separation; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000032:analysis; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014184:Transplantation, Homologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D006680:HLA Antigens; D008233:Lymphotoxin-alpha; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016572:Cyclosporine