Thanks Peter for sharing your view. I think my question (without the explanation) was not clear - I rephrased it. I know that it is good practice to weigh your mice and inject e.g. LPS according to weight. But not everyone does it and it gets through peer review. For both or either practice I would assume that a systematic study exists. Certainly they do exist in toxicology for drug medication, but I´m particularly interested in studies about weight - LPS response correlations (e.g. injection of same amount of LPS in age and sex matched mice with body weights +/- x g). Ideally this would have been done with LPS concentrations ranging from low to high to see if there is a saturation effect where mouse weight matters not.

The dose will vary according to batch, so I would advise doing your own dose response curves to a pure batch. If you are to be really careful perhaps clean the lps up when you receive it. However it is a very long time since I did this and cannot recall the protocol. Once you have your responses sorted, make sure you have a decent sized batch to work from! You could try standardising between batches by cell culture reponsiveness, but I have not had to to work to such rigour.

Hi Christoph. Attached is a dose response study. There are highly purified versions of LPS now on sale that to my knowledge wouldnt require further purification. However, batch to batch the activity of LPS varies by batch and derived source (it is a biological product), make sure you purchase enough for your study+revisions. Depending on the purpose of the study there was generally considered no reason to do a dose response - and historically inflammation was the aim, and LPS certainly delivers. That is shifting now as we finally appreciate the the response is not linear necessarily. For the dose, always relative to body weight...and you will typically see the dose given as mg/kg in good papers, and this will be altered for each animal as good practice if body weight varies.

Hope that helps. B.

Thanks for trying to help here, but it´s all a bit "off topic". I am not new to LPS and it´s pitfalls et al. I was just curios whether anyone has ever tested extensively how body-weight and LPS response correlate.

For historical reasons I have IP injected a small dose (sub-saturation, I have done dose-response experiments) the same amount of LPS (3h incubation) in mice of same genotype, sex and age but with average weight +/-2 g and not seen any correlation between body weight and induction of IL6 and Saa2 mRNA in the liver, which to me indicates that small weight differences do not matter. Before this, I would also have vigorously argued that LPS injection relative to body weight is the "golden" way...but now I am not so sure anymore...maybe doing this confounds experiments when comparing mice with different genotype and small body-weight differences (e.g. average bodyweight difference 1-2g)

Theoretically, one can think of justification for either way, so some hard data would be nice. e.g. If one injects a fixed dose, especially a sub-saturation dose, would the response-to-weight correlation be linear and hence justify the injection of LPS per kg body weight? Theoretically the LPS response at sub-saturation doses would be correlated to the number of receptors (the number of immune cells carrying TLR4 if the number of receptors per cell is constant). If weight differences are due to fat, I would not assume that immune cell number and blood volume would increase linear with body weight and that would predict a non-linear LPS response-to-weight.... . If body weight is due to real mouse size (not fat), then a linear relationship would be predicted. These are of course naive predictions, not taking into account LPS distribution etc which might impact the response and which will likely change with weight... . So hard data on this is needed and I feel reluctant to create it if it´s already around and I am just to blind to find it in the literature :-)