IL-13 inhibits TNF production but potentiates that of IL-6 in vivo and ex vivo in mice.
IL-13 was reported to inhibit the synthesis of various cytokines in vitro, including that of TNF. It has divergent effects on IL-6 production, which is increased in endothelial cells and decreased in monocytes. We studied the effect of IL-13 administration on TNF and IL-6 production in vivo in mice. IL-13 (1 microg/mouse, i.v., 10 min to 6 h before LPS) decreased LPS (100 ng/mouse, i.v.)-induced serum TNF levels by 50%, while it increased the levels of IL-6 by fourfold. IL-13 potentiated IL-1beta (100 ng/mouse, i.v.)-induced serum IL-6 levels as well as IL-1- or LPS-induced serum amyloid A. When blood from IL-13-treated mice was stimulated with LPS in vitro, TNF production was decreased fivefold, and that of IL-6 was slightly decreased. We also cultured in vitro the aorta obtained from IL-13-pretreated mice and found that they produce more IL-6 (up to sevenfold) than aorta from control mice. Little or no TNF could be detected in these samples. Thus, IL-13 in vivo inhibits serum TNF but up-regulates serum IL-6. The differential regulation of IL-6 and TNF together with the results of ex vivo experiments could be explained by hypothesizing that the cellular origins of the two cytokines are different.
Di Santo
E
E
Mario Negri Institute for Pharmacological Research, Milan, Italy.
Meazza
C
C
Sironi
M
M
Fruscella
P
P
Mantovani
A
A
Sipe
J D
JD
Ghezzi
P
P
D000818:Animals; D004347:Drug Interactions; D007275:Injections, Intravenous; D018793:Interleukin-13 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018793:Interleukin-13; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha