Ciliary neurotrophic factor combined with soluble receptor inhibits synthesis of proinflammatory cytokines and prostaglandin-E2 in vitro.
In human peripheral blood mononuclear cells, ciliary neurotrophic factor (CNTF) weakly suppressed endotoxin-induced interleukin (IL)-1 and prostaglandin E2(PGE2). Suppression of PGE2 and IL-8 synthesis was significantly greater (up to 42.6%, P < 0.05) by adding a 10-fold molar excess of soluble CNTF receptor (sCNTFR alpha). In cultured human fibroblasts, CNTF at 12 micrograms/ml did not suppress IL-1 alpha-induced IL-8. However, in the presence of a 10-fold excess of sCNTFR alpha, 300 ng/ml of CNTF suppressed IL-1 alpha-induced IL-8 by 44%. Therefore, sCNTFR alpha can confer to CNTF anti-inflammatory properties in vitro. IL-6 which, like CNTF, utilizes the gp130 signal transducer, possesses similar inhibitory effects. That CNTF and IL-6 share gp130 as a receptor component suggests that gp130 mediates these anti-inflammatory responses.
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111.
L
L
Shapiro
N
N
Panayotatos
S N
SN
Meydani
D
D
Wu
C A
CA
Dinarello
D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D015232:Dinoprostone