Bacterial
endotoxin has been shown to protect rats from lethal
hyperoxia. The structure of
endotoxin contains
diphosphoryl lipid A (DPL) as the
lipid backbone stripped of
protein and
polysaccharides. DPL is the component of the
endotoxin molecule that has been demonstrated (in previous studies) to be responsible for the immunologic, mitogenic, pyrogenic, and lethal properties of
endotoxin.
Monophosphoryl lipid A (MPL) is a nonpyrogenic, nontoxic modification of the DPL molecule that retains its immunostimulatory and mitogenic properties. We hypothesized that DPL may be the actual active component of
endotoxin that protects rats from lethal
hyperoxia. We also hypothesized that the protection from
hyperoxia that is afforded by the DPL component may be related to endogenous release of
tumor necrosis factor alpha which should allow MPL to also be protective. To test these hypotheses, we performed a series of experiments in which rats were treated with
endotoxin, DPL, MPL or vehicle and exposed to room air or
hyperoxia. We found that DPL and
endotoxin both protected rats from lethal
hyperoxia, but MPL alone was not protective. Even though MPL was not protective, DPL and MPL both increased endogenous release of
tumor necrosis factor alpha early after injection (peak DPL level, 3619 +/- 1500 pg/ml, peak MPL level, 4038 +/- 500 pg/ml). Protection in both the
endotoxin- and DPL-treated animals was associated with increases in lung
antioxidant enzyme activities. We concluded that DPL protect rats from
hyperoxia but that MPL is not protective in spite of its immunostimulatory and mitogenic effects.