More on the inflammasome

In a previous post I mentioned the inflammasome. Today I heard a talk about this by Jürg Tschopp from Lausanne who is the father of this subject in the sense that the concept and the name were invented in his lab in 2002. I learned that there are many different inflammasomes, i.e. many different protein complexes of this type. The one he concentrated on most in his talk involves a protein called NALP3. The inflammasome is involved with the occurrence or maintenance of inflammation. This may occur as a reaction to PAMPs (pathogen-associated molecular patterns) or DAMPs (danger-associated molecular patterns). The former are sensed by toll-like receptors while the others, less-well known, are associated with NOD-like receptors. He presented a very long list of diseases and other substances causing inflammation which are known or suspected to activate an inflammasome. The substances independent of pathogens mentioned included uric acid crystals, asbestos, alum (which is a constituent of some adjuvants) and nanoparticles. The typical outputs of the inflammasome are IL1 and IL18. There is a disease (or rather a group of related diseases) called CAPS (cryopyrin-associated periodic syndromes) where the inflammasome is defective and this presents an opportunity to learn about its functions.

He went on to talk about three diseases where the inflammasome may play an important role: gout, type II diabetes and MS. Gout is a disease where crystals of uric acid accumulate in the joints, causing deformity (he had some pretty horrifying pictures) and intense pain. Gout patients have attacks which can be treated with medication e.g. corticosteroids. Several days of treatment are necessary and the improvement does not last very long. He reported on successes in treating gout with anti-IL1. In that case the treatment is effective after one day and can last for a year. This means that the positive effects of one injection lasts a year! He reported similar results on anti-IL1 as a treatment for type II diabetes. The prospect he was presenting was that one injection of this substance could replace the innumerable insulin injections of a diabetes patient in a whole year. This treatment is the subject of phase 2 clinical trials by Novartis. It could even be the case that the -cells, which have been partially destroyed in this disease, start to regenerate.

In the case of MS Tschopp was linking the inflammasome with IFN therapy. Apparently this substance inhibits activation of the inflammasome. He mentioned experimantal data which show that MS patients being treated with IFN exhibit reduced inflammasome activity in response to certain antigen challenges in comparison to healthy controls. I must say that some of the things I heard in this lecture sounded almost too good to be true. The speaker himself said that he has found the success of some of the clinical trials very surprising. Maybe this is really the beginning of a major new development in medicine. Could anti-IL1 overtake anti-TNF some day?

Advertisement