Cytokine Storms

I read a lot of news articles, especially if they have to do with matters of health, new developments, etc. Sometimes this seems like a waste of time, but many times it seems to spark an interest in me to dig a little deeper. Granted, that doesn't always (or even often) happen, but it does make me think.

This article got me thinking about how little we know about how little we actually know about the function of the immune system. The idea of cytokine storms is an intriguing one to me for many reasons. I have many friends with PIDDs who have gradually started experiencing autoimmune co-morbid illness. What if... and here's a fundamental question no one knows the answer to... but what if the whole autoimmune stuff was something akin to a cytokine storm? Our bodies don't make antibodies and the rest of our immune system works overtime and produces this typhoon of overproduced crap that damages our bodies.

The things that stand out to me that gave me pause were the stuff about what happens in a cytokine storm and how the flu virus is contained in the lungs, but we experience other symptoms due to cytokine response. What if that same cytokine response is the reason people with CVID still experience lung damage while on proper IG replacement? Or what if it is the reason we have joint pain (even outside autoimmune diagnosis) Or what if.... there are many things I am thinking it makes sense for. All the repeated infections just make our bodies go completely haywire. It makes sense to me, anyway.

Better know a Cytokine: IL-25 (formerly IL-17E)

First things first. IL = Interleukin.

Now that the housekeeping is out of the way, we can get down to business. I figured it would be best to start with the cytokine that really got me into this line of thinking about the fundamental components of the immune system that we don't really know or understand well yet. I was reading a recent article from the Journal of Allergy and Clinical Immunology, like I have been known to do, and it hit me. This IL-25 thing may be a huge key to a lot of things.

How did I get there? Well, the article in question is related to non-IgE mechanics for allergic inflammation and airway reactions. I was curious about this particular phenomenon because I have many friends who produce no IgE but yet manage to have severe allergic reactions to varied things. I decided to read the article, then got hooked. I read further articles and there are some interesting things that make IL-25 unique.

IL-25 was once thought to be in the IL-17 family of cytokines because of the way it has been demonstrated to differentiate the T helper 2 lymphocytes into different immunoglobulins. It has a distinct role from IL-17A and IL-17F which eventually led to a different taxonomy. Basically, it impacts a whole different cell set. The 17 family seems to generate a distinct type of T helper cell (Th17), while IL-25 doesn't.

IL-25 does seem to have something to do with the daily problems I experience, however, because of its relation to the inflammatory processes of the body. It causes inflammation in the skin tissues as well as in the airways of the lungs. It can exacerbate asthma symptoms. In my disease experience, the inflammation of my airways has been pretty inexplicable. The antibodies aren't there to produce the problems... perhaps it is my cytokines like IL-25 instead? Hard to say.

I discussed this with my doctor yesterday and he agreed that there is a strong possibility that the allergies shown in people with immune deficiencies could well be something related to IL-25. We already know that hyper IgE syndrome (another PIDD) is a cytokine-mediated problem. Basically, the cytokines don't regulate the IgE properly. We don't really understand much of this yet, but it's super fascinating.

Cytokines

Once a month, I receive an email with the latest and greatest from the Journal of Allergy and Clinical Immunology. I like to keep up on developments and the articles usually have some useful information or send me down a useful path of research to increase my understanding of PIDDs, CIVD, and the immune system in general.

This month's journal included some research published about the cytokine now known as IL-25 (formerly IL-17E). Basically, it was found that the body produced this particular cytokine as a reaction to allergens, so it plays a role in allergic inflammation. Interesting. I hadn't previously read a great deal about cytokines, so down the rabbit hole I went.

I read several abstracts and settled on a few articles I thought were interesting, mainly focusing my work on things related to IL-25. I quickly saw that this was a broader and more interesting topic, so I expanded my search. I found this article and have been engrossed in the knowledge of each cytokine. This has expanded somewhat since 2009 when the article was published, but I'm finding it to be an interesting read.

Here are the basics of what I've learned about cytokines so far:
-Cytokines seem to be the immunological equivalent of hormones in the endocrine system.
-Researchers don't actually know much that is conclusive about these molecules.
-There are several that are responsible for B cell maturation and plasma cell differentiation.
-There are several cytokines that underlie allergic reactions and conditions - it's not just IgE, which I'd previously been lead to believe and is, seemingly, a pretty common misconception among physicians.
-Cytokines seem to be responsible at some base level for every function in the immune system.

There are several cytokines I want to talk about individually, but this is a good place to start. I will be focusing on the cytokines relevant to immunoglobulin production and autoimmune disease functions.