Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts.
In this study we have examined the effects of interleukin-10 (IL-10) on blood mononuclear cells (MNC) and on skin as well as on synovial fibroblasts. In unstimulated MNC, we found that IL-10 is a potent stimulator of interleukin-1 receptor antagonist (IL-1ra) and monocyte chemoattractant protein-1 (MCP-1) production and an inhibitor of IL-8 release. In cells exposed to IL-1 beta, it also moderately stimulated IL-1ra production and release of soluble tumor necrosis factor receptor p75 (sTNF-R p75) and inhibited IL-8 and MCP-1 production. In addition, we have evidence that the biological effects of IL-10 are not restricted to hematopoietic cells. IL-10 stimulated sTNF-R p55 dose-dependently and inhibited MCP-1 release from IL-1 beta-activated fibroblasts, whereas IL-8 production was not affected. Taken together, these findings identify novel biological actions of IL-10 on blood mononuclear and connective tissue cells which support its regulatory functions as a suppressor of inflammatory processes.
Seitz
M
M
Division of Rheumatology, University Hospital, Bern, Switzerland.
Loetscher
P
P
Dewald
B
B
Towbin
H
H
Gallati
H
H
Baggiolini
M
M
D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10