Blocking This Protein Complex Could Help Treat P. aeruginosa Infections

[paul-met-debbie]

This research of 2019 is no surprise for me. I predict that NLRP3 inhibition will not only help against specific infection with P aeruginosa. It will probably reduce the hyper-reactivity of the immune system in the cf-airways causing the excessive inflammation which lies at the base of every uncontrolable infection in cf, no matter what bacteria causes or florishes because of the inflamation.
Another study in 2016 https://www.nature.com/articles/ncomms12504 titled “Fenamate NSAIDs inhibit the NLP3 inflammasome and protect against Alzheimer’s in rodent models” proved the effectiveness of some kinds of NSAIDs in inhibiting the NLPR3 induced inflammation proces. Specifically, flufenamic acid, meclofenamic acid and mefenamic acid proved effective, while ibuprofen and celecoxib proved not effective.

Now, if one reads this older 2016-study carefully, it shows that another well known NSAID, called Diclofenac, was also effective in inhibiting the NLPR3 inflamasome. Not as effective as the other forementioned three NSAIDs that reduced the Il-1b release by 75%, but still ibuprofen showed a 25% reduction of Il-1b release (Il-1b being the important pro-inflammatory cytokine interleukin that was the subject of the study of 2019 that I am reacting to here).

Why is this no suprise to me? Well, since 5 years I am continuously taking Ibuprofen (50 mg twice a day). It started as a painkiller when I broke two ribs, and I used it for about 3 months. At that time and the three years before that, I was on a heavy schema of 6 IV’s with antibiotics every year (3 weeks each, then 5 weeks of) because of recurrent severe airway infections. To my suprise, after 6 weeks on diclofenac and still with painful ribs, it turned out that there was no exacerbation of my infection. And after 12 weeks I still didnot feel the need for an IV. I started thinking and the only thing that changed, was the diclofenac I took. So, I searched internet and found that there was enough research showing that nsaids (even ibuprofen) had a promising effect on the lungfunction of cf-patients, if administered for a longer period of time. Only these studies had not been followed up in common cf treatment protocol. Doctors were worried about side-effects (although the studies showed none of them) and it was never followed up in large fase 3 studies. Probably because these are very expensive, and there is no money to be made with diclofenac for the big pharma.

Anyway, for me it worked like a charm. Since 5 years now I had no airway exacerbation. I tried Ibuprofen before, it helped reduce symptoms like fever, but it never really had the anti-inflammatory effect that Diclofenac did have. Now these studies mentioned above give some insight in what mechanism might be behind this, and why diclofenac works, and works better than ibuprofen.

Mind you, diclofenac and other more popular current NSAIDs like ibuprofen are not innocent medication either, and generally, doctors tend to shy away from continuous use for long time. But as always, one has to balance the trade-of between effect and side-effects. In my case, being on a pretty hopeless scheme of 6 antibiotic IV’s every year (will the next IV still work?), with serious IC-antibiotics like meropenem and tazocin which also had some bad side-effects like neuropathy, not to mention the risk of increased antibiotic resistance and the practical consequences of living with almost constant IV’s, the trade-of is (so far) very beneficial. I have no side effects from Diclofenac, only I had to increase my Losec intake to protect my stomach from a slight increase in reflux.

This is only my story and experience, I am not advocating anything to anyone and I am no medical doctor. If you want to change medication talk with your doctor first.

But it would be great if new safe anti-inlammatory medication would be made that worked even better than diclofenac, based on one of these fenamate NSAIDs. So far I understand that fenamate NSAIDs are available as drug since 1980, but are not popular because of the gastro-intestinal side-effects it has (such as stomach bleeding).