PREVENTION OF ENDOTOXIN-INDUCED LETHALITY IN NEONATAL MICE BY INTERLEUKIN-13

Interleukin(IL)-13, a cytokine produced by T helper 2 (Th2) cells, is a powerful inhibitor of macrophage functions, including surface expres sion of CD14 and production of IL-1 and tumor necrosis factor (TNF)-al pha. We tested the effects of recombinant mouse(m)IL-13 in a neonatal mouse model of endotoxin shock; this is a macrophage-dependent conditi on, which is a model of neonatal sepsis in humans. mIL-13 (0.5 mu g/mo use) dramatically reduced the lethal effects of lipopolysaccharide (LP S) if administered either 24 or 4 h prior to or concomitantly with LPS challenge. This action might be mediated by multiple modulatory activ ities of IL-13 on LPS-induced cytokine secretion since, relative to co ntrol animals, the mice treated with mIL-13 had eight times lower peak blood levels of TNF. The IL-1 beta levels were also decreased, wherea s increased levels of IL-6 and IL-10 were observed at several time poi nts after LPS challenge.