Tag: Cytokines

The Scleroderma Chronicles: Chasing down the Cytokines

There was more response than I expected from my last post about my efforts to obtain a better understanding about my chronic conditions, the new drugs I was taking, and how to lower my inflammation. I offered in that post to share the links that I used to figure out what foods impact the levels of cytokines that are important in my systemic sclerosis. I’ve gotten feedback/requests for the spreadsheet with my links that I used in my adventures at PubMed.

I’ve been thinking about this for a couple of days, and I think that the most useful thing to do would be to share my process as I hunted down information about cytokines involved in my systemic sclerosis (SSc), and the cytokines that I needed to pay attention to in my diet.

I started out asking: What are the cytokines involved in systemic sclerosis? I did searches using terms like cytokines and systemic sclerosis. Here are some of the links to papers that I found.

I kept a list of the cytokines that were being measured in these studies and I finally began to get a sense of the four big players that were being measured and considered as targets for therapy: Tumor Necrosis Factor alpha (TNFα), Interferon gamma (IFN-γ), Interleukin-6 (IL-6), and Interleukin-1beta (IL-1β). You can follow the same process to research any inflammatory disease that you are interested in; you may get different results. (For example, C-Reactive Protein, called CRP for short, features in many inflammatory conditions. For little SSc me, not so much… my levels are normal.) Anyway, once I had the cytokines of interest, I did searches on all 4 of them. Here’s my info on TNF-α.

InformationSource
TNF-α is also a potent inflammatory mediator and apoptosis inducerThe role of Tumor Necrosis Factor-alpha (TNF-α) in the pathogenesis of systemic lupus erythematosus
Produced by activated immune cells (macrophages, NK cells, T-cells) known to trigger a series of various inflammatory molecules, including other cytokines and chemokines The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics
TNF-α causes other immune response cells to produce IL-1 and IL-6Tumor necrosis factor – Wikipedia
My question: What does TNF-α do?

I did the same for the other three cytokines and it turns out that for me, it is best to reduce all of them in my blood. At this point I made a little chart with the 4 cytokines at the top and began to do searches on different foods that I thought were anti-inflammatory.

FoodTNFαIFN-γIL-6IL-1β
Chile (Capsaicin)
Tart Cherry
Tomatoes (Lycopene)
Question: Which foods/supplements will decrease these cytokines levels

Now the searching gets easy. I just typed in the questions in the search bar like, “Does capsaicin reduce TNFα” or maybe “Does capsaicin reduce cytokines” and the answer would quickly pop up with some resources. Warning: the search engine will give you the pertinent text and then you are on your own as you search through these papers! If you just go with the fast answers, you will take some risks… I told my sister that tomatoes were bad because I didn’t read the whole text, and I’m not sure if she has forgiven me yet…

Anyway, here are some papers about the foods/supplements above:

If I found a source that said one of the cytokines was reduced by one of my targeted foods, I just put an “X” in that box and moved on. I was no longer recording all of the links in my excitement, and as I found info it sometimes confirmed previous finds, but not always. If I got contradictory information, I was forced to read whole papers. Ugh. Also, you might want to try a different search engine; I used Chrome on my phone and Explorer on the computer, which is another reason for incomplete links on the computer. For the three foods in the table above it ended looking like this.

FoodTNFαIFN-γIL-6IL-1β
Chile (Capsaicin)xx
Tart Cherryxx
Tomatoes (Lycopene)xxx
Question: Which foods/supplements will decrease these cytokines levels

I hope this unpacks the process that I used and helps with any searches that you decide to do that are specific to your own needs/interests.

Happy Caturday!!

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.