Increased endotoxin sensitivity following T-2 toxin treatment is associated with increased absorption of endotoxin.
Oral exposure to T-2 Toxin (T-2) in experimental animals results in a syndrome similar to that observed in endotoxemia. Endotoxins are lipopolysaccharide, outer-membrane components of gram-negative bacteria which induce acute, inflammatory responses. In the present study, several aspects of endotoxin pathophysiology were investigated in mice following simultaneous exposure to T-2 and endotoxin, including mortality, hypothermia, tumor necrosis factor-alpha (TNF-alpha) and corticosterone production, and thymic weight. The disposition of endotoxin was also assessed, Acute, simultaneous exposure to T-2 (4 mg/kg, po) and endotoxin (3 micrograms/mouse, ip) resulted in increased mortality, hypothermia, TNF-alpha production, and thymic atrophy compared to treatment with either T-2 of endotoxin alone. Pretreatment of mice with endotoxin, a regime that renders the animals resistant to the effects of endotoxin, reduced many endotoxin effects in animals treated simultaneously with T-2 and endotoxin. Upon further investigation, it was observed that T-2 increased the absorption rate of endotoxin: as the peak height of serum endotoxin increased, the time-to-peak decreased, and the area under the curve was unchanged in animals treated simultaneously with T-2 and endotoxin. It was concluded that increased endotoxin absorption accounted for the increases in mortality, hypothermia, and TNF-alpha associated with T-2 exposure.
Taylor
M J
MJ
National Institute of Environmental Health Sciences, Immunotoxicology Group, Research Triangle Park, North Carolina 27709.
Lafarge-Frayssinet
C
C
Luster
M I
MI
Frayssinet
C
C
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004347:Drug Interactions; D004731:Endotoxins / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D013605:T-2 Toxin / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D013605:T-2 Toxin; D003345:Corticosterone