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Heparin as an Anti-Inflammatory Agent
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.29.223859v1?rss=1
Authors: Litov, L., Petkov, P., Rangelov, M., Ilieva, N., Lilkova, E., Todorova, N., Krachmarova, E., Malinova, K., Gospodinov, A., Hristova, R., Ivanov, I., Nacheva, G.
Abstract:
Timely control of the cytokine release syndrome (CRS) at the severe stage of COVID-19 is key to improving the treatment success rate and reducing the mortality rate. The inhibition of the activity of the two key cytokines, IFN{gamma} and IL-6, can significantly reduce or even reverse the development of the cytokine storm. The objective of our investigations is to reveal the anti-inflammatory potential of heparin for prevention and suppression of the development of CRS in acute COVID-19 patients. The effect of low-molecular-weight heparin (LMWH) on IFN{gamma} signalling inside the stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. The mechanism of heparin binding to IFN{gamma} and IL-6 and therefore inhibition of their activity was studied by means of extensive molecular-dynamics simulations. We find that LMWH binds with high affinity to IFN{gamma} and is able to inhibit fully the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Ralpha thus preventing the formation of the IL-6/IL-6R/gp130 signalling complex. Our conclusion is that heparin is a potent anti-inflammatory agent that can be used in acute inflammatory conditions, due to its potential to inhibit both IFN{gamma} and IL-6 signalling pathways. Based on our results and available clinical observations, we suggest the administration of LMWH to COVID-19 patients in the initial stages of the acute phase. The beginning of the treatment and the dosage should be based on a careful follow-up of the platelet count and the D-dimer, IL-6, IFN, T-cells, and B-cells levels.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.29.223859v1?rss=1
Authors: Litov, L., Petkov, P., Rangelov, M., Ilieva, N., Lilkova, E., Todorova, N., Krachmarova, E., Malinova, K., Gospodinov, A., Hristova, R., Ivanov, I., Nacheva, G.
Abstract:
Timely control of the cytokine release syndrome (CRS) at the severe stage of COVID-19 is key to improving the treatment success rate and reducing the mortality rate. The inhibition of the activity of the two key cytokines, IFN{gamma} and IL-6, can significantly reduce or even reverse the development of the cytokine storm. The objective of our investigations is to reveal the anti-inflammatory potential of heparin for prevention and suppression of the development of CRS in acute COVID-19 patients. The effect of low-molecular-weight heparin (LMWH) on IFN{gamma} signalling inside the stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. The mechanism of heparin binding to IFN{gamma} and IL-6 and therefore inhibition of their activity was studied by means of extensive molecular-dynamics simulations. We find that LMWH binds with high affinity to IFN{gamma} and is able to inhibit fully the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Ralpha thus preventing the formation of the IL-6/IL-6R/gp130 signalling complex. Our conclusion is that heparin is a potent anti-inflammatory agent that can be used in acute inflammatory conditions, due to its potential to inhibit both IFN{gamma} and IL-6 signalling pathways. Based on our results and available clinical observations, we suggest the administration of LMWH to COVID-19 patients in the initial stages of the acute phase. The beginning of the treatment and the dosage should be based on a careful follow-up of the platelet count and the D-dimer, IL-6, IFN, T-cells, and B-cells levels.
Copy rights belong to original authors. Visit the link for more info