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 expression of CD14 and production of IL-1 and tumor necrosis factor (TNF)-alpha. We tested the effects of recombinant mouse(m)IL-13 in a neonatal mouse model of endotoxin shock; this is a macrophage-dependent condition, which is a model of neonatal sepsis in humans. mIL-13 (0.5 microgram/mouse) dramatically reduced the lethal effects of lipopolysaccharide (LPS) if administered either 24 or 4 h prior to or concomitantly with LPS challenge. This action might be mediated by multiple modulatory activities of IL-13 on LPS-induced cytokine secretion since, relative to control animals, the mice treated with mIL-13 had eight times lower peak blood levels of TNF. The IL-1 beta levels were also decreased, whereas increased levels of IL-6 and IL-10 were observed at several time points after LPS challenge.
Nicoletti
F
F
Institute of Microbiology, University of Milan, Italy.
Mancuso
G
G
Cusumano
V
V
Di Marco
R
R
Zaccone
P
P
Bendtzen
K
K
Teti
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D018793:Interleukin-13 / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000276:immunology / Q000401:mortality* / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004731:Endotoxins; D018793:Interleukin-13