Cytokines are immune hormones. The body produces them in response to various challenges, and they send signals to the immune system. They also affect a wide variety of endocrine, autocrine, and paracrine processes in the body. If cytokine production is too high (a ‘cytokine storm’), the results can be high levels of inflammation that can damage organs, and even cause death. If the cytokine production gets stuck in an abnormal pattern, it can cause chronic illness. There is a lot of speculation that some of the processes that create long covid involve a disturbance to the cytokine system.
“Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome.” Frontiers in Cellular and Infection Microbiology, 30 Jun 2022, PMID 35846757.
The basic findings are that IL-2 and IL-17 are elevated in long haulers, while levels of IL-4 and IL-10 are reduced. This finding opens the door to researching compounds which block the IL-2 and IL-17, or which can increase the production of IL-4 and IL-10.
These interleukins (“IL”) compounds are proteins that circulate in the blood; they can press specific buttons on the surfaces of cells, which change the behavior of those cells. Interleukins typically don’t go inside of cells, they keep circulating, they keep
The most famous cytokine is probably interferon (which is actually a group of related cytokines). In the short run, interferons can help the body resist bacterial or viral invaders. But they have side effects (including fatigue and anxiety), and long term elevation of interferons sets a person up for disease.
IL-2 (elevated in long covid)
Interleukin 2 does lots of great things. It fights infection, it helps the body resist some types of cancer. But it is elevated in long covid, and we know that a little too much can have profound side effects, including:
flu-like symptoms (headache, muscle and joint pain, fatigue)
nausea, loss of appetite
weakness or shortness of breath
drowsiness or confusion (perhaps “Brain Fog”??)
Does that sound a lot like long covid? We don’t know how much of the discomfort and disability in long covid is caused by elevated IL-2, but at this point, it seems to be a bad actor that is part of the problem.
“Interleukin 2.” Wikipedia.
IL-17 (elevated in long covid)
Interleukin 17 triggers the production of numerous pro-inflammatory compounds in the body, including: IL-6, GM-CSF, IL-1β, TNF-α), chemokines (including IL-8, GRO-α, and MCP-1), and prostaglandins (e.g., PGE2) from many cell types.
“Interleukin 17.” Wikipedia.
IL-4 (lower in long covid)
While it may be too simple to say that IL-4 is always anti-inflammatory, it is fair to say that low levels of IL-4 can increase specific inflammatory processes. IL-4 encourages young macrophages to develop into M2 repair macrophages, and these secrete IL-10 and TGF-beta … and those compounds do have anti-inflammatory effects. Boosting IL-4 on its own to abnormally high levels will typically increase allergies, so we can’t say that more is always better. But low levels of IL-4 (as have been reported in Long Covid) seem to be part of the problem.
“Interleukin 4.” Wikipedia.
IL-10 (lower in long covid)
IL-10 is generally considered an anti-inflammatory good guy. It can block the nuclear factor NF-kB and bring down elevated TNFα, IL-1β, IL-12, and IFNγ. We don't want IL-10 to be dominant when there is an active infection - those inflammatory molecules are needed to marshal our defenses. But if IL-10 is chronically low, the other messengers run amok, and it can lead to immune activation that drains health.
“Interleukin 10.” Wikipedia.
I’ll leave this post short, but there are many potential routes for lowing those cytokines that are abnormally high, and for boosting the cytokines that are unusually low. It’s not guaranteed to help, but it is an approach that makes sense, and it provides many opportunities for new posts. One of these options is Rehmannia root, which is very big in Japan (and China)… it has been a mainstay in Asian herbology for centuries, and modern research supports the idea that it can help with autoimmune diseases. Another option is the activation of the CB2 receptor using Echinacea or Cannabis.