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.

Hannah and the CoalBear: It’s Caturday Again

Hi. I’m the CoalBear (AKA Mateo)

It is sooooo hot today. It is almost 100 degrees outside, and Hannah and I are staying cool in the house. The Mother of Cats has all the windows closed and we’re too hot to look out the windows anyway. Do you notice that the Mother of Cats has been brushing out all of my downy fur? I used to have a huge ruff around my neck, and now it is almost all gone. I look a whole size smaller now. I don’t like getting brushed, but today I guess I am glad that she did it. She also cuts my nails off and I will never get used to that!!

The Mother of Cats has been knitting away on her sweater this week and look at how far she’s gotten! She is done with the first sleeve and halfway down the second one already! She has also been sewing on the quilt with Hannah.

The quilt is coming right along and should be done in just a few more days. The Mother of Cats can’t wait to get it done. Hannah kind of hopes that she is going to get to keep it for her new bed, but I think that the Mother of Cats is planning to hang it up on the wall behind her knitting chair. I ripped the old quilt down a couple of days ago (Hey! There was a moth!) and she didn’t even bother to hang it back up again. Okay, the old quilt was a Christmas themed one, so maybe she’s ready to put it away now anyway. I’m such a good boy; see how I did her a big favor?

A scary man came this week and messed around with the Mother of Cat’s oxygen machine. When he left there was new stuff left behind including this new green bottle with a snazzy carrying bag. Now the Mother of Cats has oxygen she can take with her when she goes out on errands, but mostly she stays home with us because we are so cute! She has been working on her gardens this week and they are starting to look pretty good. The first rose bloomed this week which made her really happy.

It’s her first English rose of the year!
Well, that all I have. It’s still stinking hot outside and all of the animals are asleep, so I am going to take a little nap too.

See you next week!

>^..^> CoalBear

Notes from the Mother of Cats

  • The sweater is GoldenFern by Jennifer Steingass. Hopefully I will have it done in another week or so. I’m really anxious to start another sweater but so far I’m sticking to getting this one done first.
  • I know that isn’t a good shot of the quilt, but hopefully I will have a nice picture of the completed quilt to show off next week. Hanging on the wall, where I hope it remains as long as no moths land on it. 🙂
I’m listening to this audiobook while I quilt and I just am loving it!!
  • Not only did I get oxygen-to-go this week, but I also got my injections of Evusheld, which is a combination of two monoclonal antibodies that will give me protection from Covid for at least 6 months. This is huge piece of mind for me since my doctors are dialing up my immunosuppression drug dose this month and have started me on a new immunosuppressant drug at the same time. Yay, Evusheld! With the higher dose of drugs, I won’t be able to make many antibodies of my own, so I’m glad to have the Evusheld antibodies.
  • That rose is Princess Alexandra of Kent, and it is pretty much my favorite rose in the garden right now.
  • Hannah and Mateo don’t know it but they are heading to the vet for their vaccinations and checkups next week. Sad cat day is on the way…