The Scleroderma Chronicles: Song of the Cell, Dance of the Cytokines

I’m reading a really wonderful book right now that is really speaking to me on so many levels.

This man is a BioGeek of the first order! He interweaves his experiences, patients, memories, and the history of cells together in a way that makes me green with envy. He unpacks the history of our understanding of cells by bringing those scientists to life in a way that makes me care about them; if only I could write that well. He is the teacher that I wish I had been as he reveals to us how cells work together to create complex human systems, and then ties all of that to the treatment of disease. I’m still in the first parts of the book, but I have already filled my kindle with highlights and notes.

This book was published at the exact right moment when I needed it. I have totally gone down the rabbit hole at PubMed over the last two weeks as I have read paper after paper while chasing down the major players in my chronic conditions (why am I sick, and what exactly are these new meds doing…) and how they link to inflammation. Why would anyone do something like this?

Well, it all comes down to this. I’m on high-risk drugs with some serious side effectss, and I want to make informed decisions about whether I continue taking them. I also had a run-in with elderberry juice, and was rescued by green chile; as a BioGeek I was sucked down the curiosity rabbit hole after that whole adventure. What? That doesn’t happen to you? Listen, it has been so bad I haven’t even been knitting!!!

These are the two drugs that I’m trying to understand. In his book Siddhartha Mukherjee argues that our understanding of cells, and how they work, has transformed medicine into the modern miracle that I am currently benefiting from. Drugs that directly interact with the molecular machinery of cells, the signals between them and the biochemical pathways that cells use to function, are the first of the major transformative directions modern medicine is taking in the treatment of so many pathologies such as cancer, diabetes, neurological, and autoimmune diseases such as mine.

Systemic sclerosis is really darn complicated, as it turns out, and the sequence of events that have been happening in my body are so convoluted it’s hard to track them all. It started in the cells lining my blood vessels. As those cells got injured, they sent out signals that activated parts of my immune system. Signals from the immune cells caused other cells to transform and they began to produce scar tissue… scleroderma means “hard skin”, the hallmark of my condition. Whew. Here’s a condensed version of all that if you want to torture yourself and/or fall asleep.

Let’s go back to my meds. Ambrisentan blocks a molecule that is involved in making blood vessels constrict and raises blood pressure when it is active. That molecule, endothelin, is getting turned off by the drug, and there is evidence that this will improve my exercise-induced pulmonary hypertension and will also keep it from progressing; it plays nice with my other pulmonary hypertension drug which shuts down an enzyme pathway involved in blood pressure. Ofev is my new (fairy dust) drug, and it disables some of the essential enzymes in the cells of my lungs that are involved in creating scar tissue. Interstitial lung disease is currently the leading cause of death for systemic sclerosis patients; mine is being treated by side railing the process in the cells that are essential players in the pathology.

Yay! Molecular trickery at the cellular level saves the day! I will be staying on these meds as long as I can.

Dancing to the tune of the song of immune system cells are cytokines, the messenger molecules that travel between immune system cells and other cells that they interact with. The dance is complex, with all the different messengers traveling through the blood to target cells in the body, latching on and causing the cells to take actions. Some cytokines increase inflammation, and other will shut it down. Your immune system can get dialed up or shut down, depending on what the messages are. In my travels through research papers at PubMed I focused first on what cytokines were involved in systemic sclerosis, and then I hunted for papers that had measured the levels of these cytokines when people ate different foods.

Foods that you consume can make a big difference, evidently. Elderberry made me much worse (I cried in two different doctor’s offices), and green chile saved the day. I was done doing google searches for “anti-inflammatory foods” and was going after hard data.

.What did you expect? I’m a BioGeek. OF COURSE I made a spreadsheet with the data!

Tumor Necrosis Factor alpha (TNFα) is a big driver in the whole systemic sclerosis story along with Interferon gamma (IFN-γ). They cause an increase in two more cytokines that promote inflammation, Interleukin-6 (IL-6) and Interleukin-1 beta (IL-1β). All four of these bad boys will make my inflammation worse and (probably… I’m guessing here) encourage my conditions to progress. A lot of these foods/supplements will lower the levels of these cytokines, which explains why I feel better when I eat them. ELDERBERRY increases three of these cytokines which is why I felt like death warmed over while drinking it. Google said it was anti-inflammatory… can you see why I switched to research papers and cytokines? Green chile stew has tomatoes and green chile in it (and some yummy pork and garlic!); no wonder it turned things around. I will try to eat as many of the “good” foods as I can, but I’m going to focus on ones that really shut down TNFα and IL-6. I’m ignoring the IL-10 and CRP info because it wasn’t really as well supported as the others, and I know that my CRP (C-Reactive Protein) levels are normal.

My lunch smoothie: tart cherries, raspberries, banana, spinach, yogurt, chia seed (gag) and cranberry juice. For dinner I’m having a green chile cheesy corn pudding thing that tastes pretty darn good.

Wow. Did you read all of that stuff above? You deserve a prize for perseverance.

Here’s your prize. It’s like a “Where’s Waldo” picture, but this one is Where’s Hannah!

So, there is all is. Inside my systemic sclerosis, pulmonary hypertension, interstitial lung disease self, there are all these dancing cytokines, following the song of cells. Scientists who were captured by all of this and who were entranced by the Song of the Cell have developed the drugs that are treating the two life-threatening complications of systemic sclerosis that have come my way. Inside me, the promise of the song goes on.

Time to get back to my book.

Notes:

  • Okay, I made a whole other spreadsheet with links to all of the research papers that I used to get some understanding about these cytokines, and which were important in my disease. You don’t want to see all of that, right? If you do, say so in a comment and I’ll send some links your way!
  • I became curious about what is happening with Covid patients and the cytokine storm that can cause severe symptoms. Yep. It’s happening because of TNFα, IFN-γ, and IL-6. If you catch Covid, I don’t recommend elderberry.
  • Clinical trials are currently underway to see if an IL-6 inhibitor will be an effective treatment for systemic sclerosis.
  • I’m a lucky, lucky girl. I have a degree in molecular biology, used to work in an immunology lab that focused on IL-1, was involved in a scleroderma research project, and finished up my lab days on a project looking at the impact of capsaicin on rheumatoid arthritis. I can almost understand what I’m reading on PubMed. Almost.

Author: Midnight Knitter

I weave, knit and read in Aurora, Colorado where my garden lives. I have 2 sons, a knitting daughter-in-law, a grandson and two exceptionally spoiled kittens. In 2014 I was diagnosed with a serious rare autoimmune disease called systemic sclerosis along with Sjogren's Disease and fibromyalgia.

37 thoughts on “The Scleroderma Chronicles: Song of the Cell, Dance of the Cytokines”

  1. Fascinating, Marilyn – even to a complete tyro !! I am listening currently, for about the 5th time in an effort to be able to grasp it, “The Great Cholesterol Con: The Truth About What Really Causes Heart Disease and How to Avoid It”, and so I’ve heard some of the words you use before. [grin]
    Drug R&D is a-ma-zing !!! And so are you. I mean, I know you’re a qualified .. ummm .. biological .. uhh .. remind me, sorry .. But even so, your work these days is not what you used to do, is it ?!
    No; you’re just clever. And that is definitely A Good Thing !

    1. My work these days is keeping my cats and garden happy with some knitting on the side. 🙂 After I escaped the lab I became a science teacher, then a biology teacher, and finally an instructional coach for other science teachers in my district. Being a biology teacher was the best job ever!

      1. No: your work these days is researching your physiological problems t to find out how best to cope with them – the rest is simple joy.

  2. Completely fascinating! It’s great that you can dig-in and find so much. The book sounds interesting. I feel like one of your students. I think I am headed down the Pub Med rabbit hole to see if they have anything new since I last researched my issues. Thanks for all of the information! And for inspiring us to be our own advocates!

    My family has a bunch of genetic heart issues on my father’s side of the family. There are 4 of us, siblings, and it has presented differently in each of us. I won the growing aorta lottery. On my mother’s side of the family, we have bad allergies. I have Oral Allergy Syndrome. My immune system attacks all kinds of things it shouldn’t because it is an over-eager birch pollen slayer. 🤣

    Maybe I’ll find some new information.

    1. I was so victimized for awhile there because of my disease and doctors who weren’t really qualified to treat me. It’s hard to sort it out when you don’t really know anything about your condition yourself, so… PubMed. Now things are so much better, and I feel confident in my health care providers. Oh, no. A growing aorta?!! That sounds really stressful and annoying; is there surgery on the horizon? Hugs! Allergies are just hell to deal with and I am adding over-eager bitch pollen slayer to my list of best descriptors of immune system misfunction.

  3. I want to read more. Am recovering from oral cancer surgery, radiation, bouts with oral thrush and oral lichen planus. I’m sorry you have to go thru all of what you’re dealing with! The spreadsheet you made is great. Thru my own limited understanding and research I came to the conclusions to take those supplements. But the really intriguing thing is I made a fajita filling with lots of peppers and sun dried tomatoes and it was the first thing I’ve eaten that I could actually taste and enjoy and made me feel better.

    1. Peppers and tomatoes! That is exactly what happened when I broke down and made the green chile while I was struggling so much, even though I was told to avoid spicy food. Just this week the specialty pharmacist told me to be careful with turmeric as it is anti-inflammatory, and it increases my risk of bleeding. Inside my head I heard the refrain… when will it ever end… and thanked her for the info. I then made some ginger turmeric tea.

    1. I’m talking about green chile, which is cooked using roasted green chiles, tomatoes, pork, and garlic. I buy mild green chile like Ancho, Poblano, or Anaheim because I have gastritis (which does improve as I eat chile) but hotter chiles will give you more of the active ingredient.

      1. Thank you so very much. I’m not well educated like you but after being mistreated and misdiagnosed for years by doctors I’ve started to read everything I can. We grew anaheims this year, they are my favorite. I’d like your other spreadsheet, too please. And I refuse to take the dexamethasone because I have no white blood cells and the bouts of thrush so I started making a paste of turmerics for the sorer parts of my tongue from the lichen planus.

  4. Flying my data geek flag over here to say I’d actually love to have some links if you’d care to share. I’m in the midst of trying to decide if I want to transition to a newer drug (with hopefully less side effects) than my current one for my own autoimmune issues. I find the links between foods one consumes and all the background body chemistry stuff really interesting and have always found it frustrating that there’s such a disconnect between modern medicine (where you usually are told – here take this drug and that’s all you need to do, when it is clearly is NOT all you need to do).

    As a side note, I know chia seeds aren’t for everyone but I do have a couple of suggestions/recipes, including a PB&J one that I like, so if you’d like me to send you links/notes on those because you want to try to incorporate them in another way, just let me know! Thanks for your comprehensive summary of the above!

    1. I’ve been thinking today about how to organize the links in a meaningful way that will be useful and I’m leaning towards making a post that shows the whole process. and then putting in the links that might be useful. Then maybe the recipe for the green chile…

      I’m doing better with chia seeds in the smoothies, and I found some interesting recipes online. If you have links to the recipes, I’d love to have them.

  5. I could quickly only find one study of elderberry raising cytokines and that was in vitro. I am curious as to further studies as to how the cytokine raising molecules survive the trip through the digestive system or if it is the breakdown of compounds that causes the problems. I have been going down the rabbit hole of genes and there specific alleles that may be markers of ssc

    1. That is a good question… how do any of my drugs or the active cytokine-affecting molecules survive the digestive system. I’m guessing that they are pretty small and not proteins. I became suspicious about the elderberry because I saw a little article about whether it was safe to drink if you had Covid. They were looking at cytokine storms, but I immediately was like… what! It increases cytokine levels?
      Here’s the link that I used for info: https://pubmed.ncbi.nlm.nih.gov/11399518/
      They used human monocytes in vitro, but I think that it’s okay because there was a LPS challenge for control, and it would probably be unethical to do this in actual humans depending on the amount of elderberry!

  6. SO interesting! I finally got around to reading Mukherjee’s Emperor of All Maladies about cancer and it was fascinating, informative, and understandable. I have moved his book on the gene and, now, the one on the cell up on my tbr pile. The advances in understanding of the human body and medical science that largely go unseen are truly remarkable. Hooray for scientists!

    1. I just loved the Emperor of All Maladies and knew that I wanted to read this book as soon as it came out. It does not disappoint so far. I think that his writing has improved, which is amazing.

  7. I did much the same thing when diagnosed with breast cancer in 2015. Didn’t become a biogeek in particular but became extremely knowledgeable about the disease and its treatment. I’d advise anyone to go to the original sources, the medical journals, when studying a disease or treatment. Anything else will necessarily be subject to the interpretations of less informed individuals. I’m not unbiased, however, being both a doctor’s daughter and a retired medical editor.

    (Love that purple purse/handbag in the photo!)

    1. I bought matching colored clogs to go with that handbag! 🙂 It is a Vera Bradley. I absolutely agree that as patients it is best for us to learn about our condition ourselves so we can be collaborators in our care, It can be hard sometimes when words like “survival rate” or “terminal condition” come up, but I feel that even then it is best to know. 100% agree that it is best to go to original studies and papers rather than a generalized site or something like HolisticMedicine.com. I see so much inaccurate information and claims about cures on some of these sites (take our herbal cure, for example.) Whew. You must be really rocking the medical vocabulary if you were an editor, and you probably have a great understanding of the methodology

      1. I love Vera Bradley. I’ll have to go shopping.
        “Collaborator” is the way it should be, with mutual respect and understanding, dealing with the issues together.

      2. I’m a Kaiser patient and I can see all of the physician notes online from my doctors. They even include the email chains as they brainstorm with each other about test results and treatment decisions. I love these doctors! I feel like I’m getting collaborative, interdisciplinary care from these guys, and I’m thinking that it should be like that for everyone.

      3. I have something similar, even with one doctor down at Anschutz in Aurora and one with Boulder Medical Group in Louisville.

  8. I hope your search for research papers has taken you to Google Scholar because the ordinary search engine is somewhat hopeless where they’re concerned.

  9. Wow that was really fascinating! I’m familiar with TNFa, I have several genetic variants to it that make it more active. inflammation is a bad thing, as I well know with RA. I haven’t done as deep research as you but i did some research on my raw DNA data and have a lot of increased risk for various inflammatory disorders, including lupus. I do know though that like RA, it takes a couple of things to set that off, typically genetics/environmental factors/trigger). Also high risk for Sjogrens (I believe I already have that), and alopecia. Cytokines are a big part of RA as well. Interestingly, I also have increased genetic risks to POTS and ME/CFS, which is extremely similar to long Covid. Really sucky we got saddled with this crap.

    Always praying for the best for you, keep on trucking and virtual hugs your way.

    1. I had sort of heart of TNFa, but not in the context of my scleroderma. I didn’t even use Sjogren’s in my search as the issues with the scleroderma are so in my face these days,. I donated my DNA to a Systemic Sclerosis project being done by 23 and Me, but I don’t know anything like the info that you have. Maybe I should fork out some money to see if I can get more information. 🙂

      1. I just did it an easier way. There are codes associated with each gene in the raw data and I used a website (Genetic Life Hacks) instead of just spending the time doing it all myself. I researched autoimmune and it showed all of the genes associated and where I am at increased risk.
        If I wasn’t working maybe I would spend more time on it but nah!
        Hang in there

      2. I think I could do that if I had full access to my report, but I haven’t shelled out the money yet. I think that they are still working out systemic sclerosis as they just collected DNA from patients starting in 2020, and I also suspect that the project is related to Covid as the two look a lot alike once patients hit the ICU.

  10. So interesting! Thank you so much for explaining everything so well! That sounds like a really fascinating book – will have to check it out. I really admire your research skill and your perseverance in tracking down all of this research and information 🙂 So glad you are finding things that work – from miracle medication to green chili stew! Also, lovely to see Miss Hannah on her perch 🙂

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