Need to know the concentration, dosage and preparation of LPS, I am going to test my drug whether it has any anti-sepsis action.
Dear Khan,
Please read the followings:
1-A single injection of endotoxin, or LPS, is the most commonly used toxemia model. Compared with humans, laboratory animals appear relatively insensitive to LPS and, therefore, require higher doses of LPS to produce a shock-like state. In a study directly comparing the effects of LPS, the dose required to produce similar cytokine responses was 250 times higher in mice than in humans.16 A single dose of LPS (approximately 2 ng/kg) could produce profound physiologic effects in humans (for example, increases in body temperature, systolic blood pressure, and heart rate), whereas similar signs were not seen in mice despite a much higher dose of LPS (500 ng/kg).16 The amount of LPS used to produce systemic signs in murine models varies widely, depending on the origin of LPS and mouse strain, but doses of approximately 10 mg/kg or higher are not atypical. Alternatively, doses may be reduced by sensitizing animals to LPS by coinjection of D-galactosamine.11
for more details, please use the following link:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703167/
2-Compared with humans, mice, even “normally responsive” strains, are remarkably less sensitive to the toxic or lethal effects of LPS. Thus, the dose of LPS, which leads to death in approximately half of mice (i.e., the LD50 dose) is about 1–25 mg/kg.37-39 This dose is about 1 000 000 times greater than the typical dose of LPS (2–4 ng/kg), which has been used in studies with human volunteer to induce symptoms (e.g., fever or myalgia) and the release of proinflammtory cytokines, such as TNF, into the circulation.40,41 The LD50 dose of LPS in mice is about 1000-fold to 10 000-fold greater than the dose of LPS that is required to induce severe illness and hypotension in humans.42 In other words, the roughly 40-fold difference in the dose of LPS that is required to produce toxicity or death in “normally responsive” vs. “hyporesponsive” strains of mice is orders of magnitude smaller than is the difference in LPS dose that is required to produce death or serious illness in “normally responsive” mice as compared with human beings. The biological mechanism(s) that are responsible for the enormous difference between mice and humans with respect to responsiveness to LPS remain to be fully elucidated, but recent evidence obtained by Warren and colleagues suggests that one or more factors, which are present in murine sera, but are absent (or present in much lower concentrations) in human sera, are capable of suppressing the production of pro-inflammatory cytokines by murine (or human) mononuclear cells following stimulation with LPS or other TLR agonists, such as peptidoglycan (major component of the cell wall of gram-positive bacteria), zymosan (a glucan present in the cell wall of yeast) or bacterial DNA.43 One of these factors may be the iron-binding acute phase protein, hemopexin.44 Other factors, which have yet to be identified, may be important as well. In any event, the marked discrepancy in LPS sensitivity between mice and people suggests that data obtained using murine models of sepsis may be inapplicable to the human illness.
For more details, please use the following link:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916368/
Hoping this will be helpful,
Rafik
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