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With the large amount of inflammatory cytokines involved in NASH, one would expect an overexpression of CCR5 and there is. One should not let pre-conceived notions interfere with facts.

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Maybe there is an upregulation in CCR5 surface expression, but it is probably not nearly as high as what is expressed in Tumors or in the Haplotype Matched group. We know 700 works great in Tumors and it also worked well in the HM group. However, 350mg clearly worked much better than 700mg in NASH in the typical NASH patient. 700mg worked very well in the Haplotype Matched group which points to the fact that with a high level of CCR5 surface cell expression, you want to dose it with 700mg, but with only mild to moderate increase in CCR5 expression, using 350mg works better.

The Haplotype Matched group were akin to the patients having cancer of the liver. You want to dose them with 700mg high dose LRM.

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The CC chemokines MIP-1α , MIP-1β, and RANTES and their receptors CCR1 and CCR5 were strongly upregulated in 2 experimental mouse models of fibrogenesis.
https://www.jci.org/articles/view/37444

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from here: https://www.reddit.com/r/LeronLimab_Times/com...vegf_were/

I wrote:

CCL3 also known as macrophage inflammatory protein 1-alpha ( MIP-1-alpha ). CCL3 is a cytokine belonging to the CC chemokine family that is involved in the acute inflammatory state in the recruitment and activation of polymorphonuclear leukocytes through binding to the receptors CCR1, CCR4 and CCR5.

CCL3 was sharply decreased in the entire 350mg group, increased in the 700 HM group, sharply increased in the 700mg normal group and had moderately increased in the Placebo group.

The article states that in the process of Fibrogenesis, CCL3 is upregulated. This may be true, but that is not what happened in 350mg. Fibrous tissue was being resorbed with 350mg, it was being taken up, it was not being produced as was the case, unfortunately, with the 700mg, where CCL3 was sharply increased, where there must have been, (according to your article), a sharp increase in fibrogenesis. If in fact the correlation of increasing CCL3 truly does correlate with increase in fiber.

So maybe there should be a distinction about the metabolism of Fiber. That distinction being made in the Activation of Macrophages. Possibly Fibrogenesis takes place in the M1 Classical Pathway while the Resorption of Fiber takes place in the M2 Wound Healing Alternative Pathway. I was originally thinking that all metabolism of Fiber took place in M2, but if fibrogenesis correlates with CCL3 upregulation, then fibrogenesis takes place in M1 where CCL3 is upregulated as per the definition of CCL3.

"In NASH studies, we can see correlation b/w CCL3 which is Macrophage Inflammatory Protein Alpha 1 levels and they increase in severity of NASH on biopsies. So patients in full blown NASH, show highest levels of CCL3*, but* LRM reduced CCL3 with 350mg compared to placebo from baseline from week 14."