Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and in vitro in mouse blood cells.
Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines that includes interleukin-6, interleukin-11, ciliary neurotrophic factor, leukemia inhibitory factor, and oncostatin M. As interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor were previously reported to inhibit the production of tumor necrosis factor (TNF), we studied the effect of CT-1 on serum and heart TNF levels in mice treated with lipopolysaccharide (100 ng/mouse, iv). Co-treatment with CT-1 (5 micrograms/mouse intravenously) markedly inhibit TNF production both in serum and in the heart. The effect of CT-1 seems to be direct as it also inhibited TNF production when added to whole mouse blood cultured with lipopolysaccharide. Thus, CT-1 might play a protective role in some TNF-mediated diseases.
Benigni
F
F
Laboratory of Neuroimmunology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Sacco
S
S
Pennica
D
D
Ghezzi
P
P
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood* / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C092073:cardiotrophin 1