Quote: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.
Inflammatory chemokines are induced by the CCR5 ligands and activate STAT3 which flips macrophages to M2. The inflammatory stage (M1 macrophages) is what causes the M2 macrophages to be needed for repair. High levels of M1 macrophages causing excessive apoptosis, bad. High levels of M2 macrophages causing excess collagen deposition and extracellular matrix, even worse.
Here's where the magic happens. Leronlimab knocks down the inflammatory chemokines disrupting the PI3K/AKT/mTORc/ STAT3 pathway and reverting macrophages to M1. The M1 macrophages would ordinarily induce a high inflammatory state, cell death and an even higher inflammatory state. But CCR5 blockade by leronlimab keeps that high inflammatory state from happening.
So leronlimab reduces the inflammation and reduces the M2 macrophages from creating fibrosis.
Quote:unfortunately, with the 700mg, where CCL3 was sharply increased, where there must have been, (according to your article), a sharp increase in fibrogenesis.
Was there a sharp increase in fibrosis in 700mg? Why no there wasn't, it almost made statistical significance (700 mg group (-2.73 ms vs +27.64 ms, p = 0.059).
We know increased receptor occupancy correlates directly with a decrease in inflammatory chemokines. So maybe the dichotomy between reduced fibrosis and increased CCL3 lies in Amarex hiring a testing lab who's main occupation is creating meth.
And yes CCL3 has been shown to increase the proliferation of hepatic stellate cells that aid fibrosis.
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