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 vi tro, including that of TNF, It has divergent effects on IL-6 productio n, which is increased in endothelial cells and decreased in monocytes. We studied the effect of IL-13 administration on TNF and IL-6 product ion in vivo in mice. IL-13 (1 mu g/mouse, i.v., 10 min to 6 h before L PS) 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-1 beta (100 ng/mouse, i.v.)-induced serum IL-6 levels as well as I L-1- or LPS-induced serum amyloid A, When blood from IL-13-treated mic e was stimulated with LPS in vitro, TNF production was decreased fivef old, and that of IL-6 was slightly decreased. We also cultured in vitr o the aorta obtained from IL-13-pretreated mice and found that they pr oduce 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 inh ibits serum TNF but up-regulates serum IL-6. The differential regulati on of IL-6 and TNF together with the results of ex vivo experiments co uld be explained by hypothesizing that the cellular origins of the two cytokines are different.