If somebody was having issues with a weakened immune system, and also dealing with a chronically higher baseline level of inflammation, are there any known ways to strengthen the immune system while reducing or at least not increasing baseline inflammation? Is that even possible or is some level of inflammation unavoidable?
Would it depend on the specific inflammatory factors that are already causing the higher baseline response?
I know there’s some research about running reducing inflammation, but it also triggers some inflammation? Is the acute inflammation triggered by running tied to longer term reductions in inflammation?
Over the last year, I’ve been constantly sick with back to back colds that turn into sinus infections and require antibiotics. I literally just finished my 6th round. Never had this issue before the last year.
The best I can describe it is like constantly having the flu, but the symptoms seem to always be coming and going. It’s definitely worse and more persistent when I’m actually sick with a virus or sinus infection, but I also just haven’t had my normal level of energy/really felt like myself since COVID. It also seems like when I push myself, the symptoms tend to flare up. Like you know how when you feel like crap sometimes, but you push yourself to exercise and you feel better? I don’t have that anymore. If I exercise when I’m already feeling like shit, then I just feel even shittier for a few days.
I got COVID in March, and since then I’ve had an abnormally high platelet count that seems to be climbing, high ESR, low complement C4, normal complement C3, normal CRP. Everything else is 100% normal, except I had a positive ANA that was right at 1:80 and flagged as high. When it was retested again a few weeks later, all the other blood work was the same, but the ANA was negative.
I often get really weird temperature spikes (not actual fevers but enough to be noticeable and uncomfortable usually~99.9 °F) that are accompanied by brain fog, really bad fatigue, and very stiff and achy joints. Nobody has been able to tell me what’s going on other than I seem to be dealing with “some inflammation” probably related to COVID.
I’ve seen a PC multiple times, a respiratory therapist, and an allergist. I couldn’t get in to see an ENT until April 2026. I’m finally seeing a rheumatologist next week, but I’m not all that hopeful since I have very vague symptoms, my ANA was negative when retested, and all the other high values in my blood work don’t really seem to point to anything specific, other than “some inflammation.”
I’ve been told repeatedly to just treat the symptoms in the meantime. I have noticed when I take azithromycin (but not other antibiotics) for my sinus infections, I seem to feel more energetic, productive, and more like my old self than I have any other time since COVID. I know that it also has immunomodulatory and antiinflammatory effects, so I’m wondering if I might be able to find similar relief for my symptoms without an antibiotic.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4186419/
https://www.nature.com/articles/s41390-021-01613-4
https://www.nature.com/articles/s41467-025-64778-0
I’m not familiar with COVID, but it does sound to me like you’ve got long COVID. I’ve got no advice on that front - frankly, I don’t think anybody really knows what’s up with that. I get the impression that that’s why the advice that you’ve received so far are primarily focused on treating symptoms.
If your hypothesis is correct that your antibiotic is helping through its immunomodulatory effects, then it looks like it’s acting primarily through inhibiting cytokine production. Messing with cytokines will certainly affect your ability to fight off infections, since that’s how your body signals to immune cells that there’s something wrong. Of course, immunity is all about balance, and you don’t need to block cytokine signaling completely in order to decrease it to manageable levels… A brief search shows that there are inhibitors for TNFa, which based on your links seem to be what you’re leaning towards as the molecular mediator.
Have you considered bringing this up to your doctor? I’m not sure how feasible it would be to do a “trial run” with one of these inhibitors to see if it helps your symptoms. However, it may be simple enough to ask for a blood test to measure the amounts of different cytokines in your blood. My understanding (don’t trust me on this - I’m not a clinician) is that standard blood tests don’t typically measure cytokines, which is potentially why your blood tests so far haven’t been able to pick anything up out of the ordinary. That would at least help rule in/out any possible causes.
I will also point out an alternative hypothesis that might be worth considering - it could be that the antibiotic is depleting your microbiome, which would reduce the same cellular pathways that your antibiotic is said to inhibit due to your cells being in less contact with bacteria. Have you tried other antibiotics, and did they have a similar effect?
Thanks, this is seriously one of the most helpful answers I’ve gotten in the last year!
I will ask about the possibility of trying a modulator and getting blood work for my cytokine levels. I’ve also been trying to find other things that might target the same pathway. There seems to be some evidence that turmeric/curcumin also acts as an anti-inflammatory by inhibiting TNF-a/NF-kB. That has also been somewhat helpful, but not as much as azithromycin.
Yes, I’ve been prescribed other antibiotics, but none have had the same effect. Most of the time I’m prescribed amoxicillin which does clear up the sinus infection, but doesn’t help with any of the other symptoms, and seems to actually increase my stiffness/achy joints
The second most recent sinus infection I had was probably the most severe, and I was given amoxicillin plus topical mupirocin. The Mupirocin actually seemed like it might have helped some with the brain fog, but not the other symptoms.
I think at one point I was prescribed clindamycin, and I kind of remember it being more helpful for my symptoms than amoxicillin, but not anywhere nearly as helpful as azithromycin.
Interestingly though it looks like clindamycin may be involved in the same pathway https://pubmed.ncbi.nlm.nih.gov/37429145/
That makes sense, but unfortunately in a frustratingly unhelpful way. NF-kB is the central mediator of cellular immunity. What that means is that everything that needs an immune response triggers NF-kB and everything immunity-related gets activated due to NF-kB. Likewise, TNFa is the prototypical pro-inflammatory cytokine. It’s remarkably good at triggering immune responses in a wide variety of cells, and every immune response that I know involves TNFa in some way.
In other words, having inflammatory symptoms be caused by NF-kB>TNFa is less of a “that’s an interesting pathway” and more of a “yeah, of course NF-kB and TNFa would be involved, what’s new?”
The concern is that we don’t really know what’s activating NF-kB in the first place, and so as a result you can’t really fix the core problem. And because NF-kB and TNFa are involved in basically every immune process, it’s hard to tell if these proteins are the ones actually responsible for causing your symptoms. You’d be operating on a hunch, essentially. Though I will say that your unusually nondescript and broad symptoms do seem roughly in line with what I would expect from TNFa signaling.
All that to say, I’m not a doctor and I have no experience with translating knowledge into practicable therapies, so definitely talk to a doctor about it. But TNFa is very easy to detect in your blood, and if TNFa is causing your symptoms, then it’s really easy to just check to see if you’ve got high TNFa in your blood when you’re taking the antibiotics vs. when you’re not. If you had the money, you could even buy a test kit yourself and get an answer in a single day, assuming you know how to use the kit
Yeah but not every anti-inflammatory is going to inhibit NF-kB equally, so having something to target with inhibition is more helpful than just advice to avoid inflammation.
https://pubmed.ncbi.nlm.nih.gov/15489888/
Unfortunately an educated hunch is about as much as I think I can expect as of now bc the only doctor who isn’t just dismissing me is kind of at that point, and since he can’t figure it out, he’s open to suggestions.
And also having TNF-a levels tested isn’t anything somebody has suggested previously. It took me going back and forth between March and April to even get in to see an allergist to measure my tryptase levels bc I assumed it was histamines. Turns out it wasn’t.