Experimental study of hemarisin in protecting mice from lethal endotoxin shock and inhibiting production of proinflammatory cytokines

Objective To investigate the effects of hemarisin(lipopolysaccharide from Bacillus prodigiosus) on protecting mice from lethal endotoxin shock,and explore the underlying mechanism of action.Methods Models of lethal endotoxin shock and endotoximia were reproduced in KM mice by intraperitoneal(ip) administration of lipopolysaccharides(endotoxin) from Pseudomonas aeruginosa in doses of 60mg/kg or 10mg/kg respectively.Exudate cells from peritoneal carity activated by endotoxin were used as in vitro inflammatory cell model.Levels of interleukin-1β(IL-1β),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA).Results The survival rate was found to be higher in mice prophylactically treated with 100 or 50 U/kg hemarisin(0.5h before endotoxin administration)(70% and 55%) than in model group(10%,P < 0.01).The serum levels of IL-1β,IL-6 and TNF-α were significantly lower in 100 or 50 U/kg hemarisin-treated mice(0.5h before endotoxin administration) than in model groups(P < 0.05).Hemarisin(20U/mL) alone showed slight stimulatory effect to peritoneal exudate cells in producing IL-1β,IL-6 and TNF-α in vitro(P < 0.05).When used in combination with endotoxin,however,hemarisin(20 and 10 U/mL) showed antagonistic effect against endotoxin in inducing the secretion of IL-1β,IL-6 and TNF-α in vitro(P < 0.05).Conclusions Hemarisin shows a slight promotive effect on production of IL-1β,IL-6 and TNF-α when it is used alone.When used in combination with endotoxin,however,hemarisin may inhibit endotoxin from stimulating the production of proinflammatory cytokines and antagonize the endotoxin toxicity.