Ivermectin Inhibits LPS-induced Production of Inflammatory Cytokines and Improves LPS-induced Survival in Mice

Objective and design:

To investigate whether ivermectin, a semi-synthetic derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro.

Materials and methods:

C57BL/6 mice were administered ivermectin (or saline) orally and challenged intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine macrophages were stimulated with LPS at 1 microg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss) and interleukin-6 (IL-6) in serum from mice and supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB) translocation with subunit p65 was evaluated by immunocytochemical analysis.

Results:

Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-alpha, IL-1ss and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS.

Conclusions:

The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation.

[-] TrumpLyftAlles | 1 points | May 24 2020 19:23:53

Here another drug that inhibits elevation of NF-kB is proposed for covid19.

From Covid-19: what treatments are being investigated? (2020/03/26)

Cromolyn Sodium May Attenuate Covid-19 SARS and Systemic Complications and May Be Useful Prophylactically.

COVID 19 activates NF-kB pathway, like MERS and SARS-COV (3). SARS-COV virus has been studied in vitro and in mice and was shown to promote inflammatory mediators in vitro and in vivo through actions on NF-kB. Levels of NF-kB were higher in lungs of (recombinant SARS (rSARS)-infected mice. Inhibitors of NF-kB improved survival of BALB/c mice and reduced rSARS-COV-induced inflammation, without influencing viral titers.

FUCK, the reference for the assertion that COVID-19 activates NF-kB is the (2013) article "Inhibition of NF-κB-mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival".

The author proposes that cromolyn may prevent inflammation. It's another old familiar drug like ivermectin. There are no studies of covid-19 + cromolyn at ClinicalTrials.

Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.

[-] TrumpLyftAlles | 1 points | May 24 2020 19:32:07

Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival (2014)

Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.

[-] TrumpLyftAlles | 1 points | May 24 2020 19:42:12

Preventing 'cytokine storm' may ease severe COVID-19 symptoms (2020/05/21)

What causes a cytokine storm?

When macrophages (and some other kinds of immune cells) detect virus particles, they send out alert messages by releasing various proteins known as cytokines. Those cytokines recruit other immune cells to the scene - an inflammatory response that, in moderation, helps the body fight off a virus. But macrophages can also release other signaling molecules, called catecholamines, that amplify this response further, triggering the release of more cytokines. The result is a runaway feedback loop, like a snowball getting bigger as it barrels down a hill.

"It seems that once this process starts, there's this inability to properly switch it off," says Maximilian Konig, a rheumatologist at Hopkins who is helping to coordinate the trial.

In the trial, COVID-19 patients will take gradually increasing doses of an alpha blocker called prazosin, sold under the brand name Minipress, over six days.

[-] [deleted] | 1 points | May 24 2020 20:28:37

[deleted]

[-] TrumpLyftAlles | 1 points | May 24 2020 20:45:52

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

This is a literature review, relevant because it asserts that modulation (? reduction) of NF-kB reduces cytokine storms (really rough paraphrase).

This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-kB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-kB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.