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s_r_constantin's profile
Sarah Constantin
Sarah Constantin
Sarah Constantin
@s_r_constantin

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Sarah Constantin

@s_r_constantin

Math/ML/data-science person now working on solving aging...and helping with COVID19?! Founder, LRI and Daphnia Labs. Married to @oscredwin

Be
srconstantin.posthaven.com
Joined February 2019

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    1. Tony Breu‏ @tony_breu Apr 17
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      5/ Result: macrolides prevent the release of proinflammatory protein toxins and virulence factors such as bacterial adhesins and biofilm. This can occur at sub-minimal MICs and with organisms typically resistant to macrolides (e.g., pseudomonas). https://www.ncbi.nlm.nih.gov/pubmed/17848373 pic.twitter.com/Yz197LIAT8

      1 reply 13 retweets 92 likes
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    2. Tony Breu‏ @tony_breu Apr 17
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      6/ To understand the immune system-directed mechanism recall another feature of macrolides: They accumulate inside cells, including immune cells (at concentrations 90-350x higher than in serum). For at least 28 days! https://www.ncbi.nlm.nih.gov/pubmed/12208321 pic.twitter.com/6H4M7nVxVI

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    3. Tony Breu‏ @tony_breu Apr 17
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      7/ In fact, the intensity of anti-inflammatory activity correlates with cellular accumulation. One study found that IL-6 and prostaglandin E2 suppression were highest when the cellular concentration of the macrolide (or other compound) was highest. https://www.ncbi.nlm.nih.gov/pubmed/21473915 pic.twitter.com/ocWv2zqrEv

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    4. Tony Breu‏ @tony_breu Apr 17
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      8/ What are macrolides DOING inside cells that leads to their anti-inflammatory properties? Again: A LOT (see pic 2 in tweet 3 for a list). For this thread, I'll review one mechanism: suppression of IL-8.

      1 reply 11 retweets 54 likes
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    5. Tony Breu‏ @tony_breu Apr 17
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      9/ What is IL-8? 💥a potent neutrophil chemoattractant (i.e., chemokine)💥 In patients with chronic lung disease, IL-8 leads to neutrophil accumulation in the airways and to progressive lung injury. https://www.ncbi.nlm.nih.gov/pubmed/7927669 pic.twitter.com/djNTlp9E2S

      2 replies 10 retweets 67 likes
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    6. Tony Breu‏ @tony_breu Apr 17
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      10/ There is evidence that macrolides decrease sputum levels of IL-8 (and other inflammatory markers, like TNF-alpha). https://www.ncbi.nlm.nih.gov/pubmed/15252191 pic.twitter.com/dUvC5YdBjo

      1 reply 10 retweets 61 likes
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    7. Tony Breu‏ @tony_breu Apr 17
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      11/ And going back to panbronchiolitis, one study found decreased neutrophil chemotactic activity and neutrophils counts in patients treated with erythromycin. Decreased neutrophil recruitment may lead to the beneficial effects seen in tweet 2. https://www.ncbi.nlm.nih.gov/pubmed/7924482 pic.twitter.com/Cf5Ax4Sf60

      1 reply 10 retweets 48 likes
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    8. Tony Breu‏ @tony_breu Apr 17
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      12/ There is A LOT more to the immunomodulatory effects of macrolides. There may even be a biphasic effect: 🔷Early: stimulation of neutrophils (↑degranulation, ↑oxidative burst) and ↓IL-8. 🔷Late: ↓oxidative burst; ↑neutrophil apoptosishttps://www.ncbi.nlm.nih.gov/pubmed/24631273 

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    9. Tony Breu‏ @tony_breu Apr 17
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      13/ If macrolides have anti-inflammatory effects, might this mechanism provide beneficial in viral infections? Maybe. One RCT of azithromycin in infants with respiratory syncytial virus bronchiolitis found: ↓upper airway IL-8 levels ↓days wheezing https://www.ncbi.nlm.nih.gov/pubmed/25458910 pic.twitter.com/u4xZNuujah

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    10. Tony Breu‏ @tony_breu Apr 17
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      14/ Independent of the anti-inflammatory properties, macrolides may have direct anti-viral activity. For example, azithromycin reduced Zika proliferation in glial cells. This may explain why some have attempted to use azithromycin for SARS-CoV-2. https://www.ncbi.nlm.nih.gov/pubmed/27911847 pic.twitter.com/i1oE9LNKJh

      3 replies 12 retweets 85 likes
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      Sarah Constantin‏ @s_r_constantin Apr 17
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      Replying to @tony_breu

      This is not scientific but I've seen enough neat anti-inflammatory/neuroprotective stuff with macrolides that I just *like* 'em. Good vibes. Also azithromycin does inhibit SARS-CoV-2 in vitro.

      10:01 AM - 17 Apr 2020
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      • Elissa Franz Ronay Tony Breu
      1 reply 0 retweets 3 likes
        1. New conversation
        2. Tony Breu‏ @tony_breu Apr 17
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          Replying to @s_r_constantin

          Can you share a link to the study for SARS-CoV-2?

          1 reply 0 retweets 0 likes
        3. Sarah Constantin‏ @s_r_constantin Apr 17
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          Replying to @tony_breu

          https://www.biorxiv.org/content/biorxiv/early/2020/04/05/2020.04.03.023846.full.pdf …

          1 reply 1 retweet 0 likes
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