Tolerance to hyperoxia usually requires an increase of lung antioxidant enzyme (AOE) activity. We used rats with different degrees of tolerance to > 95% O2 to evaluate the importance of individual AOEs for tolerance; we also explored the regulation of AOE gene expression. During exposure of adult rats to > 95% O2, lung manganese superoxide dismutase (MnSOD) activity fell approximately 50% despi...

In previous publications we presented evidence that a bacterial endotoxin is present in the blood and tissues of the animal in hemorrhagic shock; and that if shock is sufficiently prolonged this endotoxin prevents a sustained response to infusion of all the blood removed, so that death follows soon thereafter (1, 2). Since the ingestion of circulating endotoxins, and, by inference, their detoxi...

The phenomenon of endotoxin tolerance has been widely investigated, but to date, the molecular mechanisms of endotoxin tolerance remain to be resolved clearly. The discovery of the Toll-like receptor (TLR) family as the major receptors for lipopolysaccharide (LPS) and other bacterial products has prompted a resurgence of interest in endotoxin tolerance mechanisms. Changes of cell surface molecu...

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, ...

The pyruvate kinase (PK) activity of mouse liver increases after injection of endotoxin. It decreases in animals given cortisone alone and remains essentially unchanged in those given cortisone and endotoxin at the same time. CCl4 causes an increase in liver PK activity, but neither it nor endotoxin changes the activity of muscle PK. Addition of octonoate to liver homogenates inhibits the activ...

The phenomenon of early endotoxin tolerance, which is induced by sublethal injection of lipopolysaccharide (LPS), results in a protracted period of hyporesponsiveness that is most profound at 3 to 4 days after injection and is marked by reduced cytokine production after a challenge injection of LPS. Early endotoxin tolerance is also induced by the nontoxic LPS derivative monophosphoryl lipid A ...

Additional evidence is presented affirming the role of the intestinal pool of endotoxin in producing irreversibility in prolonged hemorrhagic shock. The fact that coliform-free rabbits tolerate exposure to a degree and duration of hemorrhagic shock which is lethal for rabbits that possess the normal flora, and that these tolerant rabbits lose their tolerance when E. coli are introduced into the...

Overwhelming inflammation triggered by systemic infection in bacterial sepsis contributes to the pathology of this condition. Toll-like receptors (TLRs) are important in early septic inflammation. As a safeguard, the innate immune system has evolved to counter excessive inflammation through the induction of "tolerance." In endotoxin tolerance, TLR signaling is inhibited and/or attenuated by mul...

Ovalbumin (OVA)-sensitized wildtype (WT) and endotoxin-resistant (ER) mice developed similar degrees of airways eosinophilia and serum OVA-specific IgE levels after acute aerosolized OVA challenge. WT mice demonstrated methacholine hyperreactivity, whereas ER mice showed no change in responsiveness. With chronic aerosolized OVA challenge, both WT and ER mice developed local tolerance, with reso...