Aspirin, NSAIDs, cell death and the treatment of arthritis and interstitial cystitis

While doing some research on interstitial cystitis Google uncovered an extraordinary claim by the Cleveland Clinic’s Raymond Rackley:

Microsoft Word - Transcript for IC Video.doc

… exposure to TNF−α produces a dysfunctional activation pattern in IC urothelial cells that leads to cellular apoptosis…

Aberrant NF−κB signaling activation may be responsible for the imbalance of apoptotic and survival mechanism of the bladder epithelium that gives rise to the pathogenesis of IC … asking all IC patients to avoid aspirin or aspirins like products such as NSAIDs that block normal NF- B signaling …

I can’t tell when this transcript was created, there’s no date information on the PDF. As of Feb 2016 Rackley has 71 publications, but the only one that might lead in this direction was from 2011. I don’t think there have been any publications out of this particular video presentation.

The claim is extraordinary for two reasons. The first is that interstitial cystitis is a common cause of significant suffering, we have no good treatments (see also), and patients often use NSAIDs or even aspirin (which acidifies urine, for some that might help). If this claim were true those people should all switch to acetaminophen.

The other reason, of course, is that the transcript notes that aspirin and NSAIDS (ibuprofen, etc) have a significant effect on the mechanisms that influence cell death (apoptosis). This is mentioned as though it were common knowledge, but it was a surprise to me. Perhaps it shouldn’t have been, I know here has been a suspicion for at least 10 years that NSAIDs slow tendon injury healing. I’m also aware of epidemiology studies of an inverse association between colon cancer and aspirin use, and recently the USPSTF added colorectal cancer prevention to its draft aspirin use guidelines.

I suppose, in retrospect, if aspirin reduces the risk of colorectal cancer it may well do so by empowering our cellular level anti-cancer controls (vs. say, altering the microbiome). One way to empower those controls is to bias our cellular monitoring systems towards more aggressive cellicide (apoptosis) — and away from healing.

This has occurred to researchers. A search on apoptosis and aspirin returns 181 results starting in 1995 and accelerating in 2008 (NSAIDs) with a flurry of publications in the past few years. So among researchers, the idea that aspirin and NSAIDs shift our cellular systems away from healing and towards apoptosis (for better or worse) is probably not so surprising.

For clinicians however, this is potentially significant. We use aspirin for heart disease of course, but only in modest doses. More importantly, we use NSAIDs extensively for arthritic conditions where we may want more rather than less healing. (Not to mention interstitial cystitis).

It would be good to know how real this effect is. As Emily reminds me it is perilous to extrapolate from basic research to clinical practice. Even so, I would suggest people suffering from interstitial cystitis may want to consider acetominophen, assuming their liver is in good health.