IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia: correlation with down-modulation of TNF-alpha, IFN-gamma, and IL-12 production.
IL-13 is a potent down-modulator of macrophage proinflammatory activity in vitro, similar in this context to the anti-inflammatory cytokines IL-4 and IL-10. Since IL-10 effectively confers protection to mice from LPS-induced lethal endotoxemia through inhibition of proinflammatory cytokine production, we investigated whether IL-13 may also be capable of providing protection in this experimental model of endotoxic shock. A single injection of recombinant murine IL-13 (rmIL-13; 0.5-10 microg) significantly increased survival in a dose-dependent manner when a lethal i.p. injection of endotoxin was administered to BALB/c mice. This effect appeared to be IL-13 specific, since survival was not affected in mice that received heat-inactivated rmIL-13. rmIL-13 provided significant protection to mice even when given 30 min after LPS injection; however, this protection decreased in a time-dependent manner as the administration of rmIL-13 was delayed by 1, 2, and 5 h following LPS injection. The protective effect of IL-13 was correlated with significant decreases in the production of the inflammatory mediators TNF-alpha, IFN-gamma, and IL-12 as well as a decrease in the anti-inflammatory mediator IL-10. Our data suggest that IL-13 provides protection from LPS-induced lethal endotoxemia in a manner that is similar to but independent from that of IL-10, and therefore can be added to the list of cytokine immunomodulators that might be beneficial in the treatment of septic shock.
Muchamuel
T
T
DNAX Research Institute, Palo Alto, CA 94304, USA.
Menon
S
S
Pisacane
P
P
Howard
M C
MC
Cockayne
D A
DA
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D015536:Down-Regulation / Q000276:immunology*; D019446:Endotoxemia / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D018793:Interleukin-13; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma