Bacterial endotoxin both enhances and inhibits the toxicity of Shiga-like toxin II in rabbits and mice

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Abstract
The ability of bacterial lipopolysaccharide (LPS) to enhance the toxicity of Shiga-like toxin II (SLT-II) was investigated in rabbits and mice. Rabbits were continuously infused with 0.5 50% lethal dose (LD50) of SLT-II per day. Rabbits that received a 30-micrograms/kg dose of LPS (0.02 LD50) on day 3 of infusion were significantly more likely to die than were rabbits receiving SLT-II only. Rabbits receiving SLT-II and a lower dose of LPS (3 micrograms/kg) did not die but lost an average 3.3% +/- 1.0% of initial body weight during the first 5 days of infusion, compared with weight gains of 4.2% +/- 0.6% and 17.1% +/- 0.9% for rabbits receiving only SLT-II or LPS, respectively. Rabbits that were pretreated with LPS 20 h before challenge with a single dose of SLT-II showed highly significant protection from both the diarrheagenic and lethal effects of SLT-II. Pretreatment of endotoxin-responsive C3H/HeN mice protected the animals from challenge with an LD50 but not an LD100 of SLT-II. LPS enhanced the lethal toxicity of SLT-II for C3H/HeN mice when it was given at 8 or 24 h but not 0 or 72 h after SLT-II challenge. LPS did not affect the lethal toxicity of SLT-II for endotoxin-resistant C3H/HeJ mice. These results suggest that LPS enhances the effects of SLT-II in vivo. Since cecal changes that increase mucosal permeability occur in response to SLT in rabbits, this synergy may be directly relevant to disease processes.