Comments on: Alum, take 2: A better answer

By: Justin

Justin — Sun, 19 Jun 2011 17:31:23 +0000

i’m not as scientific as i’d like to be but right off the bat, uric acid signaling our immune system is just wrong. for uric acid to trigger something is just really physically painful. thanks for shedding light on this. i always enjoy your posts and expanding my knowledge on health and science.

By: Pranav

Pranav — Mon, 14 Feb 2011 18:02:50 +0000

it has been mentioned that alum activates the the innate immune system, my question is, how is a better immune response against an Ag conjugated with alum generated?
(forgive me if my question sounds elementary, i am a student of basic immunology)

By: A general rule for (some) adjuvants | Mystery Rays from Outer Space

A general rule for (some) adjuvants | Mystery Rays from Outer Space — Sun, 22 Feb 2009 01:59:44 +0000

[...] A couple of years ago1 it was discovered that the natural adjuvant uric acid stimulates immunity through an intracellular sensor called the Nalp3 inflammasome. Last year, a bunch of groups showed the the commonly-used adjuvant alum — also kind of crystalline — acts through the Nalp3 inflammasome. 2 Then it turned out that silca causes the inflammation associated with silicosis via, right, the Nalp3 inflammasome. 3 (I talked about this in several places, including here.) [...]

By: María Luján

María Luján — Wed, 22 Oct 2008 02:35:13 +0000

Hi, yes, there is published this and the results are important:
Arthritis Rheum. 2008 Mar;58(3):888-94.
Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases?Verma D, Lerm M, Blomgran Julinder R, Eriksson P, Söderkvist P, Särndahl E.
… RESULTS: Mutation analysis of the patient’s genes encoding NALP3, ASC, and TUCAN revealed variations in the NLRP3 (Q705K) and CARD-8 (C10X) genes. The allele frequencies of these single-nucleotide polymorphisms (SNPs) in the population were 6.5% and 34%, respectively. .. CONCLUSION: Our results indicate that the patient’s symptoms were due to elevated levels of IL-1beta, since treatment with anakinra effectively abolished the symptoms. The compound SNPs may explain the increased IL-1beta levels and inflammatory symptoms observed, but further studies are needed to reveal a functional relationship. The prevalence of the polymorphisms (4% of the population carry both SNPs) in the general population may suggest a genetic predisposition for common inflammatory disorders.

By: Silicosis parallels alum | Mystery Rays from Outer Space

Silicosis parallels alum | Mystery Rays from Outer Space — Wed, 25 Jun 2008 23:51:52 +0000

[...] Flavell’s group showed that alum adjuvant — also (sort of) crystalline — also acts through the Nalp3 inflammasome.2 And now, a paper just out in PNAS says that crystalline silica causes silicosis by acting [...]

By: Mystery Rays from Outer Space - Meddling with things mankind is not meant to understand. Also, pictures of my kids » Adjuvants: Quality as well as quantity

Thu, 19 Jun 2008 14:50:49 +0000

[...] explanation for alum’s mechanism of action — though that explanation is at least partly rendered obsolete by the recent paper7 from Richard Flavell’s group), and direct stimulation of T cell clones [...]

By: iayork

iayork — Fri, 30 May 2008 11:14:01 +0000

Kay, as always, the short answer is likely “Don’t know”. For uric acid — I’ve seen micrographs (not published, I think) of monosodium urate crystals mixed with dendritic cells. The MSU crystals are long, needle-like things and they actually seem to penetrate the cells, sticking right through them. Bizarrely this doesn’t seem to kill the cells. I find it hard to believe that this is actually what is happening — maybe it’s some kind of illusion, and the crystals end exactly at the membrane; or maybe the cells really are dead, though assays don’t indicate it — but it’s at least conceivable that it’s real and the MSU can physically enter the cytosol.

I’ve never seen alum crystals and I don’t know if they look anything like this.

By: Kay

Kay — Fri, 30 May 2008 10:33:09 +0000

This is all very nice, but how do the Alum crystals get to the inflammasome? Unlike the TLRs, the NLRs are cytoplasmic and I have always liked the idea that NALP-based recognition is mainly for endogenous stimuli. I must say that Jurg was also rather vague on this issue in his gout paper (sorry Jurg, but I guess that you are not reading this anyway, or are you?)