Lysozyme regulates LPS-induced interleukin-6 release in mice.
Bacterial lipopolysaccharide (LPS) stimulates the production and release of endogenous mediators [e.g., tumor necrosis factor (TNF), interleukins-1 and -6 (IL-1 and IL-6), and Platelet Activating Factor [PAF] responsible for the pathophysiologic changes and the mortality associated with sepsis. We recently demonstrated that lysozyme (LZM) bound to LPS (LZM-LPS complex) suppresses LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in vivo. In the present study, we investigated the effect of LZM-LPS complex formation on LPS-induced IL-6 production, both in vitro and in vivo. With the addition of LZM-LPS complex, TNF-alpha and IL-6 release was significantly reduced compared with that by LPS in a dose-dependent manner in mouse macrophage-like cells, RAW264.7. IL-6 production in serum by LPS in carrageenan (CAR)-primed mice peaked at 2 hr following injection. LZM-LPS and LZM-Escherichia coli cell complex (as 1 microgram of LPS per mouse) released significantly reduced concentrations of IL-6 in serum (P < 0.01 and P < 0.001 versus CAR-pretreated LPS- or cell-injected mice). These results emphasize the important role of LZM in vivo in the neutralization of endotoxin. However, in the case of IL-6, by administration of a lethal dose of LPS (as 100 micrograms of LPS per mouse), the IL-6 level was reduced by LZM, but a significant concentration of IL-6 was still released; although the TNF- alpha concentration was negligible in this experimental condition. Thus, it is suggested that LZM might regulate the systemic inflammation induced during Gram-negative bacterial infections by inhibiting the release of cytokines in serum.
Takada
K
K
Laboratory for Immunopharmacology of Microbial Products, Tokyo College of Pharmacy, Japan.
Ohno
N
N
Yadomae
T
T
D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D004926:Escherichia coli; D015850:Interleukin-6 / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009113:Muramidase / Q000378:metabolism / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D009113:Muramidase