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Posted On: 04/26/2020 10:15:22 PM
Post# of 145890
JC_Greg,
Yes, it would be nice for him to address this. Maybe it will be addressed in their NEJM article.
With the IL-6 numbers completely out-of-control that we saw: IL-6 1000.1, 522.6, 2506.6, 8175.1, 83 and knowing that IL-6 is a homeostasis regulator, no wonder that we are seeing the results we are seeing. Below some excerpts from a very interesting paper on the subject:
https://onlinelibrary.wiley.com/doi/pdf/10.10...01.03061.x
And so on. The message here is that elevated IL-6 levels can indeed produce the clotting/stroke that has been observed.
It follows that if Leronlimab can reduce these chaotic levels if IL-6 the secondary effects this produces will be ameliorated as well.
Quote:
Although you addressed the myocardial complications from another source, I'd really love to hear Dr BP weigh in on this topic, hopefully as soon as tomorrow's CC.
The recent clotting/stroke reports have been a bit disconcerting to me -especially stories like this about relatively young mild/asymptomatic patients suddenly suffering strokes.
Yes, it would be nice for him to address this. Maybe it will be addressed in their NEJM article.
With the IL-6 numbers completely out-of-control that we saw: IL-6 1000.1, 522.6, 2506.6, 8175.1, 83 and knowing that IL-6 is a homeostasis regulator, no wonder that we are seeing the results we are seeing. Below some excerpts from a very interesting paper on the subject:
https://onlinelibrary.wiley.com/doi/pdf/10.10...01.03061.x
Quote:
Effects of IL-6 on tissue factor may also be mediated indirectly through CRP, an acute-phase protein released by hepatocytes after IL-6 stimulation (Heinrich et al, 1990). CRP at concentrations found during inflammation has been shown to increase tissue factor procoagulant activity 75-fold in studies using monocyte cultures
Quote:
The synthesis of the potent inhibitor of coagulation, antithrombin (AT) may also be influenced by IL-6. AT production has been shown to be inhibited by both IL-6 and IL-1 in cultured hepatocytes (Niessen et al, 1997) and acquired AT deficiency may occur in sepsis as part of the acute-phase response
Quote:
IL-6 contributes further to haemostasis by enhancing platelet production as elegantly reviewed by Burstein (1997). IL-6 has been shown to promote megakaryocyte maturation in the absence of other growth factors. Also, it possibly stimulates megakaryocyte proliferation. Administration of IL-6 has been shown to result in a significant increase in the platelet count. IL-6 also alters platelet function and enhances thrombin-induced platelet activation. Thus by stimulating the mechanisms of both primary and secondary haemostasis, IL-6 appears to be an important mediator of the development of a stable fibrin clot.
Quote:
It has been shown recently that elevated levels of IL-6 are independently linked to markers of endothelial cell activation such as tPA, thrombomodulin and VWF (Yudkin et al, 1999). Heterogeneity in endothelial cell function in different tissues cannot be discerned in these in vivo studies, and it is only possible to speculate about their relationship with local thrombotic disease such as myocardial infarction. However, in vitro studies of endothelial cells from different tissues are limited by the need for soluble IL-6 receptor and also the removal of these cells from their normal microenvironment through which many interactions may occur.
Quote:
The possible role of IL-6 in thrombotic disease, particularly myocardial infarction, has generated a great deal of interest recently and there are several excellent reviews on this subject (Tracy, 1999; Yudkin et al, 2000). IL-6 has other effects, in addition to modulating haemostasis and endothelial cell function, which may contribute to the development of coronary heart disease
And so on. The message here is that elevated IL-6 levels can indeed produce the clotting/stroke that has been observed.
It follows that if Leronlimab can reduce these chaotic levels if IL-6 the secondary effects this produces will be ameliorated as well.
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