When the mortality is about 50%, is any significance related to their mortality due to body weight?
The rate of loss is more correlative to mortality than the absolute numbers, unless it goes below 30% of control.
The amount and duration of weight loss depends on the dose of LPS. With a dose that induces 50% mortality there should be very signifcant weight loss and I would expect the mice that survive to still be significantly leaner at 7 days compared to their baseline body weight.
Actually, it is a basic tenet of the severe acute inflammatory response, in this case induced by endotoxin (endotoxemia), that a sequence of events follows. If they stop eating, it makes no difference because they go into a catabolic response that is not offset by anabolism for some time. I don't know what happens between the TLR receptor and cell signaling. The main feature has to be that C-reactive protein, transferrin, and alpha-1 acid-glycoprotein are increased (acute phase reactants), the liver repriotizes synthetic activities, and transthyretin and retinol-binding protein decrease. The classic physiological effect is depletion of glycogen stores in liver rapidly, a more gradual development of lactic acidemia as there is impaired entry to the Krebs cycle, and breakdown of lean body mass to provide gluconeogenic precursors. When 40% of lean body mass is lost, death ensues (from repiratory failure, and from cardiovascular collapse). This is mediated at first by catacholamines causing glycogenolysis in the liver (not muscle), and then by increased corticosteroids geneting the proteolysis.
Thank you all of your valuable suggestions to me, but I need to clariify one thing - is it possible that mice lose weight after endotoximia induction, due to proteolysis of their skletal muscle?
There is no question that there is a relationship between loss of lean body mass and mortality, and I could see why the rate of loss (dose related) predicts earlier mortality. Loss of intercostal muscles would be easily measured by taking the chest circumference, and loss of limb muscle would be tied to weakness at gate, so you could measure the rate on a contrived treadmill.
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