Opposite effects of interleukin-13 and interleukin-12 on the release of inflammatory cytokines, cytokine inhibitors and prostaglandin E from synovial fibroblasts and blood mononuclear cells.
We examined the effects of interleukin-12 (IL-12) and interleukin-13 (IL-13) on cytokine, cytokine inhibitor and prostaglandin E (PGE) release from synovial fibroblasts and blood mononuclear cells (MNC). In resting synovial fibroblasts, we found that IL-13 is an inhibitor of IL-8 and PGE release. A significant decrease of PGE synthesis caused by IL-13 was also observed in tumor necrosis factor (TNF)-alpha-stimulated synovial fibroblasts, whereas IL-12 had no regulatory effects on these cells. In resting and cytokine-stimulated MNC, IL-13 markedly inhibited IL-1 beta, IL-8 and monocyte chemoattractant protein-1 (MCP-1) release and potently stimulated interleukin-1 receptor antagonist (IL-1ra) synthesis. In contrast, IL-12 stimulated the production of IL-1 beta and MCP-1 in TNF-alpha-stimulated MNC and inhibited IL-1ra synthesis in cytokine-stimulated cells. These findings identify novel biological actions of IL-12 and IL-13 on connective tissue and on blood mononuclear cells which indicate their regulatory functions as enhancer and suppressor of inflammatory processes, respectively.
Seitz
M
M
Division of Rheumatology, University Hospital, Bern, Switzerland.
Loetscher
P
P
Dewald
B
B
Towbin
H
H
Baggiolini
M
M
D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018793:Interleukin-13; D016209:Interleukin-8; D011458:Prostaglandins E; D012795:Sialoglycoproteins; D018664:Interleukin-12