Hype control for neuroinflammation

This is Hype Control, can I help you?

I’d like to report a hype emergency in progress, please. It’s burning out of control!

What kind of hype, sir?

Medical hype about neuroinflammation. There are a lot of people saying it can be caused by stress alone and can explain practically anything! I, um … I may also have contributed to this myself …

It’s good that you called, sir. It’s going to be okay. You’ve confessed so we can worry about punishing you later. But all that matters right now is that we get this thing contained. I’m going to transfer you to a specialist. Please hold for Woodburn et al.

[Insipid music 🎶]

This is Woodburn. We wrote a paper about this, and we can definitely curb your enthusiasm. What’s the situation?

Hi. I’m a health journalist, and I wrote about immunology a little…

A common mistake. Never write about immunology! But let’s see if we can control the damage. So what exactly did you say?

I may have gotten a little overexcited about the power of “neuroinflammation” to explain some cases of chronic pain and illness, including my own. But it’s not just me! Everyone is doing it! It’s extremely popular!

We know, we know. How exactly did you explain it?

Well, people can feel really awful and amazingly exhausted when we are seriously sick or injured, but not because viruses or violence directly cause those symptoms. A lot of them are a “side effect” of immune system botheration. The system is of course mind-bogglingly more complicated than we can wrap our heads around, an evolutionary palimpsest with many cryptic layers.

Yes, yes, this is all fine so far. Please continue.

One of its many functions is an inflammation of the nervous system specifically that sucks the life out of us, probably an adaptive feature that protects us from ourselves: it makes us feel too gross for risky behaviour like moving around, standing up, or even speaking. Organisms that are too weary to do anything get hurt less and spread infections less.

That’s … actually rather brilliant. If only all independent science journalists were so articulate and insightful.

Um, thanks, but… [sobs] … but I didn’t stop there…

Oh. Yes, well, that was predictable. We probably know what’s coming, but please confirm.

So that nasty feeling could also occur to some degree without any obvious provocation, and it may also be triggered solely by perceived threats to health.

Like stress. You blamed neuroinflammation on psychological stress, didn’t you?

Maybe. Yes. A little. Hypothetically! I prefaced everything I said with “perhaps” and “maybe” and “turns out possibly” and “may or may not contain trace amounts of hype”!

Which is just ass-covering. You were still amplifying the idea. Dammit, man! This is how hype fires start! Do you see the error of your ways now?

Yes. That’s why I called Hype Control! I feel terrible.

Please state for the record the precise nature of your error.

Well, implying that stress has that kind of power is actually kind of ridiculous, isn’t it? Major trauma and pathology are, well, major. Stress just isn’t really in the same league. Nothing most people will ever deal with is going to provoke the same degree of total immune system freakout that you see with people who are nearly killed by injury or illness. In fact, it’s so different that it probably can’t be considered the same phenomenon.

Excellent! Yes, that’s just it. As we wrote: “Preclinical research demonstrates that neuro-immune responses to stress are distinct from CNS disease, injury, or infection and should not be characterized as neuroinflammation.” Please update your social media followers and newsletter subscribers immediately, and we’ll be lenient at your Hype Control sentencing. Maybe.

This has been an extremely silly dramatization of lessons learned from:

“The semantics of microglia activation: neuroinflammation, homeostasis, and stress”
Woodburn et al. J Neuroinflammation. Volume 18, Number 1, 258. Nov 2021.

Neuroinflammation is an extremely complex niche of immunology, and there is plenty more than could be said about this paper. However, this one main idea seemed so critical that it was worth dedicating a post to it — and a fun one to make it memorable.

I don’t think this necessarily means that stress and neuroinflammation have nothing whatsoever to do with each other. I think it's even conceivable that some relatively ordinary stresses — if enough of them pile up, for long enough — could still provoke something that starts to resemble frank neuroinflammation.

Even if that never happens, there could still be overlap between neuro-immune responses to stress and frank neuroinflammation in response to injury and disease.

But it is an extremely important caveat that true, full-blown “neuroinflammation” is defined by some well-known characteristics, and very unlikely to occur even with severe stresses, if at all.

Vocabulary denouement

The density of the scientific literature on neuroinflammation is dazzling. Here’s a typical title: “SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression.” Phew!

Ubiquitination? That’s a fun term, derived from ubiquitin, a small protein found in basically all eukaryotic life — so it’s “ubiquitin” because it’s ubiquitous!